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112 results on '"Wong, Yien Ning Sophia"'

2. Identification of urine derived lymphocytes as a non-invasive measure of the tumour immune microenvironment in bladder cancer

Author

Wong, Yien Ning Sophia

Abstract

Despite the advances in systemic immunotherapy with immune checkpoint blockade, only a small fraction of patients with bladder cancer respond to this treatment. This highlights a need to better understand drug resistance and identify rational immunotherapeutic combinations. This thesis explores the immune checkpoint landscape of the bladder tumour microenvironment (TME) in three main groups of patients with bladder cancer: non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC), and metastatic urothelial bladder cancer. The immune checkpoint landscape between NMIBC and MIBC in the bladder TME was very similar, but distinct to peripheral blood. Interestingly, I observed the presence of urine-derived lymphocytes (UDLs) in NMIBC as previously described, but also in MIBC. We identified UDLs as a readily accessible source of T cells in 32 patients with MIBC, and demonstrated that UDLs have a remarkably similar immunological T cell phenotype and TCR repertoire to tumour infiltrating lymphocytes (TILs) in patients with MIBC. Interestingly, patients with MIBC who were found to have high urinary lymphocytes, at the time of cystectomy, in particularly high expression of PD-1 (PD-1hi) on CD8+, had a reduced recurrence free survival. Furthermore, I developed a lab protocol for the in vitro expansion of cryopreserved UDLs. Expanded UDLs produced IFNg and TNFa when restimulated with autologous tumour samples. In addition, with collaborative efforts, we explored the antigenic specificity of T cells and observed the presence of neoantigen reactive T cells (NARTs) in the peripheral blood of a single patient. Finally, in nine patients with metastatic bladder cancer, I showed a poor prognostic association in patients with high UDL CD3+ count and an exhaustive phenotype of CD8+ PD-1hi UDLs as detected at the end of treatment, which could also be tracked longitudinally in metastatic patients undergoing systemic therapy. Taken together, the data suggest a role for UDLs as an immune biomarker to track response to systemic therapy. However, this requires a large prospective study to validate these findings. Crucially, the data above highlight the importance of incorporating UDL analysis in all future studies with a view to integrating into routine clinical practice in patients with bladder cancer.

Published
2021

3. Nivolumab and ipilimumab for metastatic prostate cancer with an immunogenic signature: The NEPTUNES multi-centre two-cohort, biomarker-selected phase 2 trial.

Author

Linch, Mark David, primary, Leone, Gianmarco, additional, Wong, Yien Ning Sophia, additional, Jones, Robert J., additional, Sankey, Peter, additional, Josephs, Debra Hannah, additional, Crabb, Simon J., additional, Harris, Louise, additional, Tasnim, Aniqa, additional, Rashid, Memuna, additional, Quezada, Sergio A., additional, Ensell, Leah, additional, Jayaram, Anuradha, additional, Kayani, Mahaz, additional, Pritchard, Colin C., additional, Freeman, Alex, additional, Haider, Aiman, additional, Attard, Gerhardt, additional, Swanton, Charles, additional, and Marafioti, Teresa, additional

Published
2024
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4. Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vaccinated and unvaccinated patients with cancer in Europe: results from the retrospective, multicentre, OnCovid registry study

Author

Evans, Joanne S, Swallow, Judith, Chung, Chris, Patel, Meera, Dettorre, Gino, Ottaviani, Diego, Chowdhury, Amani, Merry, Eve, Chopra, Neha, Lee, Alvin JX, Sng, Christopher CT, Yu, Tamara, Shawe-Taylor, Marianne, Bain, Hamish DC, Wong, Yien Ning Sophia, Galazi, Myria, Benafif, Sarah, Dileo, Palma, Earnshaw, Irina, Patel, Grisma, Wu, Anjui, Soosaipillai, Gehan, Cooper, Lee, Andaleeb, Ramis, Dolly, Saoirse, Apthorp, Eleanor, Srikandarajah, Krishnie, Jones, Eleanor, Van Hemelrijck, Mieke, Moss, Charlotte, Russell, Beth, Chester, John, Loizidou, Angela, Piccart, Martine, Cruz, Claudia A, Reyes, Roxana, Segui, Elia, Marco-Hernández, Javier, Viladot, Margarita, Eremiev, Simeon, Fort-Culillas, Roser, Garcia, Isabel, Liñan, Raquel, Roqué Lloveras, Ariadna, Harbeck, Nadia, Wuerstlein, Rachel, Henze, Franziska, Mahner, Sven, Felip, Eudald, Pous, Anna, D'Avanzo, Francesca, Scotti, Lorenza, Krengli, Marco, Marrari, Andrea, Delfanti, Sara, Maconi, Antonio, Betti, Marta, Tonini, Giuseppe, Di Fazio, Giuseppina Rita, Tondini, Carlo, Chiudinelli, Lorenzo, Franchi, Michela, Libertini, Michela, Bertulli, Rossella, Baggi, Alice, Tovazzi, Valeria, Ficorella, Corrado, Porzio, Giampiero, Saponara, Maristella, Filetti, Marco, Zoratto, Federica, Paoloni, Francesco, Berardi, Rossana, Guida, Annalisa, Bracarda, Sergio, Iglesias, Maria, Sanchez de Torre, Ana, Tagliamento, Marco, Colomba, Emeline, Pommeret, Fanny, Pinato, David J, Aguilar-Company, Juan, Ferrante, Daniela, Hanbury, Georgina, Bower, Mark, Salazar, Ramon, Mirallas, Oriol, Sureda, Anna, Plaja, Andrea, Cucurull, Marc, Mesia, Ricard, Townsend, Sarah, Jackson, Amanda, Dalla Pria, Alessia, Newsom-Davis, Thomas, Handford, Jasmine, Sita-Lumsden, Ailsa, Vincenzi, Bruno, Bertuzzi, Alexia, Brunet, Joan, Lambertini, Matteo, Maluquer, Clara, Pedrazzoli, Paolo, Biello, Federica, Sinclair, Alasdair, Bawany, Samira, Khalique, Saira, Rossi, Sabrina, Rogers, Lucy, Murphy, Cian, Belessiotis, Katherine, Carmona-García, M Carmen, Sharkey, Rachel, García-Illescas, David, Rizzo, Gianpiero, Perachino, Marta, Saoudi-Gonzalez, Nadia, Doonga, Kris, Fox, Laura, Roldán, Elisa, Gaidano, Gianluca, Ruiz-Camps, Isabel, Bruna, Riccardo, Patriarca, Andrea, Martinez-Vila, Clara, Cantini, Luca, Zambelli, Alberto, Giusti, Raffaele, Mazzoni, Francesca, Caliman, Enrico, Santoro, Armando, Grosso, Federica, Parisi, Alessandro, Queirolo, Paola, Aujayeb, Avinash, Rimassa, Lorenza, Prat, Aleix, Tucci, Marco, Grisanti, Salvatore, Mukherjee, Uma, Diamantis, Nikolaos, Fusco, Vittorio, Generali, Daniele, Provenzano, Salvatore, Gennari, Alessandra, Tabernero, Josep, and Cortellini, Alessio

Published
2022
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5. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study

Author

Swallow, Judith, Chung, Chris, Dettorre, Gino, Chopra, Neha, Lee, Alvin JX, Sng, Christopher CT, Wong, Yien Ning Sophia, Galazi, Myria, Benafif, Sarah, Dileo, Palma, Patel, Grisma, Wu, Anjui, Sinclair, Alasdair, Soosaipillai, Gehan, Jones, Eleanor, Diamantis, Nikolaos, Mukherjee, Uma, Jackson, Amanda, Piccart, Martine, Pommeret, Fanny, Colomba, Johann, Colomba-Blameble, Emeline, Prat, Aleix, Cruz, Claudia A, Reyes, Roxana, Segui, Elia, Marco-Hernández, Javier, Tabernero, Josep, Aguilar-Company, Juan, Ruiz-Camps, Isabel, Fox, Laura, Garcia Illescas, David, Mirallas, Oriol, Roldán, Elisa, Carbó, Anna, Garcia, Isabel, Wuerstlein, Rachel, Mesia, Ricard, Maluquer, Clara, D'Avanzo, Francesca, Tonini, Giuseppe, Provenzano, Salvatore, Tovazzi, Valeria, Ficorella, Corrado, Queirolo, Paola, Giusti, Raffaele, Mazzoni, Francesca, Zoratto, Federica, Tucci, Marco, Berardi, Rossana, Guida, Annalisa, Bracarda, Sergio, Iglesias, Maria, Pinato, David J, Bower, Mark, Scotti, Lorenza, Patel, Meera, Colomba, Emeline, Dolly, Saoirse, Loizidou, Angela, Chester, John, Zambelli, Alberto, Dalla Pria, Alessia, Ottaviani, Diego, Chowdhury, Amani, Merry, Eve, Salazar, Ramon, Bertuzzi, Alexia, Brunet, Joan, Lambertini, Matteo, Tagliamento, Marco, Pous, Anna, Sita-Lumsden, Ailsa, Srikandarajah, Krishnie, Seguí, Elia, Generali, Daniele, Grisanti, Salvatore, Pedrazzoli, Paolo, Rizzo, Gianpiero, Libertini, Michela, Moss, Charlotte, Evans, Joanne S, Russell, Beth, Harbeck, Nadia, Vincenzi, Bruno, Biello, Federica, Bertulli, Rossella, Liñan, Raquel, Rossi, Sabrina, Carmona-García, Maria Carmen, Tondini, Carlo, Baggi, Alice, Fotia, Vittoria, Parisi, Alessandro, Porzio, Giampero, Saponara, Maristella, Cruz, Claudia Andrea, García-Illescas, David, Felip, Eudald, Roqué Lloveras, Ariadna, Sharkey, Rachel, Earnshaw, Irina, Ferrante, Daniela, Gaidano, Gianluca, Patriarca, Andrea, Bruna, Riccardo, Sureda, Anna, Martinez-Vila, Clara, Sanchez de Torre, Ana, Cantini, Luca, Filetti, Marco, Rimassa, Lorenza, Chiudinelli, Lorenzo, Franchi, Michela, Krengli, Marco, Santoro, Armando, Van Hemelrijck, Mieke, Newsom-Davis, Thomas, Gennari, Alessandra, and Cortellini, Alessio

Published
2021
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6. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

Author

Gault, Abigail, Agnieszka, Michael, Bedair, Ahmed, Ghaus, Aisha, Akingboye, Akinfemi, Maynard, Alec, Pawsey, Alexander, Suwaidan, Ali Abdulnabi, Okines, Alicia, Massey, Alison, Kwan, Amy, Ferreira, Ana, Angelakas, Angelos, Wu, Anjui, Tivey, Ann, Armstrong, Anne, Madhan, Annet, Pillai, Annet, Poon-King, Ashley, Kurec, Bartlomiej, Usborne, Caroline, Dobeson, Caroline, Thirlwell, Christina, Mitchell, Christian, Sng, Christopher, Scrase, Christopher, Jingree, Christopher, Brunner, Clair, Fuller, Claire, Griffin, Clare, Barrington, Craig, Muller, Daniel, Ottaviani, Diego, Gilbert, Duncan, Tacconi, Eliana, Copson, Ellen, Renninson, Emily, Cattell, Emma, Burke, Emma, Smith, Fiona, Holt, Francesca, Soosaipillai, Gehan, Boyce, Hayley, Shaw, Heather, Hollis, Helen, Bowyer, Helen, Anil, Iris, Illingworth, Jack, Gibson, Jack, Bhosle, Jaishree, Best, James, Barrett, Jane, Noble, Jillian, Sacco, Joseph, Chacko, Joseph, Chackathayil, Julia, Banfill, Kathryn, Feeney, Laura, Horsley, Laura, Cammaert, Lauren, Mukherjee, Leena, Eastlake, Leonie, Devereaux, Louise, Melcher, Lucinda, Cook, Lucy, Teng, Mabel, Hewish, Madeleine, Bhattacharyya, Madhumita, Choudhury, Mahbuba, Baxter, Mark, Scott-Brown, Martin, Fittall, Matthew, Tilby, Michael, Rowe, Michael, Alihilali, Mohammed, Galazi, Myria, Yousaf, Nadia, Chopra, Neha, Cox, Nicola, Chan, Olivia, Sheikh, Omar, Ramage, Paul, Greaves, Paul, Leonard, Pauline, Hall, Peter S, Naksukpaiboon, Piangfan, Corrie, Pippa, Peck, Rahul, Sharkey, Rachel, Bolton, Rachel, Sargent, Rebecca, Jyothirmayi, Rema, Goldstein, Robert, Oakes, Roderick, Shotton, Rohan, Kanani, Ruhi, Board, Ruth, Pettengell, Ruth, Claydon, Ryan, Moody, Sam, Massalha, Samah, Kathirgamakarthigeyan, Sangary, Dolly, Saoirse, Derby, Sarah, Lowndes, Sarah, Benafif, Sarah, Eeckelaers, Sarah, Kingdon, Sarah, Ayers, Sarah, Brown, Sean, Ellis, Shawn, Parikh, Shefali, Pugh, Sian, Shamas, Simon, Wyatt, Simon, Grumett, Simon, Lau, Sin, Wong, Yien Ning Sophia, McGrath, Sophie, Cornthwaite, Stephanie, Hibbs, Stephen, Tillet, Tania, Rabbi, Taslima, Robinson, Tim, Roques, Tom, Angelis, Vasileios, Woodcock, Victoria, Brown, Victoria, Peng, YingYing, Drew, Yvette, Hudson, Zoe, Lee, Lennard Y W, Cazier, Jean-Baptiste, Starkey, Thomas, Briggs, Sarah E W, Arnold, Roland, Bisht, Vartika, Booth, Stephen, Campton, Naomi A, Cheng, Vinton W T, Collins, Graham, Curley, Helen M, Earwaker, Philip, Fittall, Matthew W, Gennatas, Spyridon, Goel, Anshita, Hartley, Simon, Hughes, Daniel J, Kerr, David, Lee, Alvin J X, Lee, Rebecca J, Lee, Siow Ming, Mckenzie, Hayley, Middleton, Chris P, Murugaesu, Nirupa, Newsom-Davis, Tom, Olsson-Brown, Anna C, Palles, Claire, Powles, Thomas, Protheroe, Emily A, Purshouse, Karin, Sharma-Oates, Archana, Sivakumar, Shivan, Smith, Ashley J, Topping, Oliver, Turnbull, Chris D, Várnai, Csilla, Briggs, Adam D M, Middleton, Gary, and Kerr, Rachel

Published
2020
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7. The T cell differentiation landscape is shaped by tumour mutations in lung cancer

Author

Ghorani, Ehsan, Reading, James L., Henry, Jake Y., Massy, Marc Robert de, Rosenthal, Rachel, Turati, Virginia, Joshi, Kroopa, Furness, Andrew J. S., Ben Aissa, Assma, Saini, Sunil Kumar, Ramskov, Sofie, Georgiou, Andrew, Sunderland, Mariana Werner, Wong, Yien Ning Sophia, Mucha, Maria Vila De, Day, William, Galvez-Cancino, Felipe, Becker, Pablo D., Uddin, Imran, Oakes, Theres, Ismail, Mazlina, Ronel, Tahel, Woolston, Annemarie, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai J., Wilson, Gareth A., Litchfield, Kevin, Conde, Lucia, Guerra-Assunção, José Afonso, Blighe, Kevin, Biswas, Dhruva, Salgado, Roberto, Lund, Tom, Bakir, Maise Al, Moore, David A., Hiley, Crispin T., Loi, Sherene, Sun, Yuxin, Yuan, Yinyin, AbdulJabbar, Khalid, Turajilic, Samra, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S., McGranahan, Nicholas, Chain, Benny, Swanton, Charles, and Quezada, Sergio A.

Published
2020
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11. Escape from nonsense-mediated decay associates with anti-tumor immunogenicity

Author

Litchfield, Kevin, Reading, James L., Lim, Emilia L., Xu, Hang, Liu, Po, Al-Bakir, Maise, Wong, Yien Ning Sophia, Rowan, Andrew, Funt, Samuel A., Merghoub, Taha, Perkins, David, Lauss, Martin, Svane, Inge Marie, Jönsson, Göran, Herrero, Javier, Larkin, James, Quezada, Sergio A., Hellmann, Matthew D., Turajlic, Samra, and Swanton, Charles

Published
2020
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12. Data from Clinical Portrait of the SARS-CoV-2 Epidemic in European Patients with Cancer

Author

Pinato, David J., primary, Zambelli, Alberto, primary, Aguilar-Company, Juan, primary, Bower, Mark, primary, Sng, Christopher C.T., primary, Salazar, Ramon, primary, Bertuzzi, Alexia, primary, Brunet, Joan, primary, Mesia, Ricard, primary, Seguí, Elia, primary, Biello, Federica, primary, Generali, Daniele, primary, Grisanti, Salvatore, primary, Rizzo, Gianpiero, primary, Libertini, Michela, primary, Maconi, Antonio, primary, Harbeck, Nadia, primary, Vincenzi, Bruno, primary, Bertulli, Rossella, primary, Ottaviani, Diego, primary, Carbó, Anna, primary, Bruna, Riccardo, primary, Benafif, Sarah, primary, Marrari, Andrea, primary, Wuerstlein, Rachel, primary, Carmona-Garcia, M. Carmen, primary, Chopra, Neha, primary, Tondini, Carlo, primary, Mirallas, Oriol, primary, Tovazzi, Valeria, primary, Betti, Marta, primary, Provenzano, Salvatore, primary, Fotia, Vittoria, primary, Cruz, Claudia Andrea, primary, Dalla Pria, Alessia, primary, D'Avanzo, Francesca, primary, Evans, Joanne S., primary, Saoudi-Gonzalez, Nadia, primary, Felip, Eudald, primary, Galazi, Myria, primary, Garcia-Fructuoso, Isabel, primary, Lee, Alvin J.X., primary, Newsom-Davis, Thomas, primary, Patriarca, Andrea, primary, García-Illescas, David, primary, Reyes, Roxana, primary, Dileo, Palma, primary, Sharkey, Rachel, primary, Wong, Yien Ning Sophia, primary, Ferrante, Daniela, primary, Marco-Hernández, Javier, primary, Sureda, Anna, primary, Maluquer, Clara, primary, Ruiz-Camps, Isabel, primary, Gaidano, Gianluca, primary, Rimassa, Lorenza, primary, Chiudinelli, Lorenzo, primary, Izuzquiza, Macarena, primary, Cabirta, Alba, primary, Franchi, Michela, primary, Santoro, Armando, primary, Prat, Aleix, primary, Tabernero, Josep, primary, Gennari, Alessandra, primary, Avanzi, Gian Carlo, primary, Bellan, Mattia, primary, Castello, Luigi Mario, primary, Martinez, Maria, primary, Mollà, Meritxell, primary, Pirisi, Mario, primary, Scotti, Lorenza, primary, and Swallow, Judith, primary

Published
2023
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13. Supplementary Data from Clinical Portrait of the SARS-CoV-2 Epidemic in European Patients with Cancer

Author

Pinato, David J., primary, Zambelli, Alberto, primary, Aguilar-Company, Juan, primary, Bower, Mark, primary, Sng, Christopher C.T., primary, Salazar, Ramon, primary, Bertuzzi, Alexia, primary, Brunet, Joan, primary, Mesia, Ricard, primary, Seguí, Elia, primary, Biello, Federica, primary, Generali, Daniele, primary, Grisanti, Salvatore, primary, Rizzo, Gianpiero, primary, Libertini, Michela, primary, Maconi, Antonio, primary, Harbeck, Nadia, primary, Vincenzi, Bruno, primary, Bertulli, Rossella, primary, Ottaviani, Diego, primary, Carbó, Anna, primary, Bruna, Riccardo, primary, Benafif, Sarah, primary, Marrari, Andrea, primary, Wuerstlein, Rachel, primary, Carmona-Garcia, M. Carmen, primary, Chopra, Neha, primary, Tondini, Carlo, primary, Mirallas, Oriol, primary, Tovazzi, Valeria, primary, Betti, Marta, primary, Provenzano, Salvatore, primary, Fotia, Vittoria, primary, Cruz, Claudia Andrea, primary, Dalla Pria, Alessia, primary, D'Avanzo, Francesca, primary, Evans, Joanne S., primary, Saoudi-Gonzalez, Nadia, primary, Felip, Eudald, primary, Galazi, Myria, primary, Garcia-Fructuoso, Isabel, primary, Lee, Alvin J.X., primary, Newsom-Davis, Thomas, primary, Patriarca, Andrea, primary, García-Illescas, David, primary, Reyes, Roxana, primary, Dileo, Palma, primary, Sharkey, Rachel, primary, Wong, Yien Ning Sophia, primary, Ferrante, Daniela, primary, Marco-Hernández, Javier, primary, Sureda, Anna, primary, Maluquer, Clara, primary, Ruiz-Camps, Isabel, primary, Gaidano, Gianluca, primary, Rimassa, Lorenza, primary, Chiudinelli, Lorenzo, primary, Izuzquiza, Macarena, primary, Cabirta, Alba, primary, Franchi, Michela, primary, Santoro, Armando, primary, Prat, Aleix, primary, Tabernero, Josep, primary, Gennari, Alessandra, primary, Avanzi, Gian Carlo, primary, Bellan, Mattia, primary, Castello, Luigi Mario, primary, Martinez, Maria, primary, Mollà, Meritxell, primary, Pirisi, Mario, primary, Scotti, Lorenza, primary, and Swallow, Judith, primary

Published
2023
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14. Supplementary Figure from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, primary, Childs, Alexa, primary, Akarca, Ayse U., primary, Dhami, Pawan, primary, Vaikkinen, Heli, primary, Conde, Lucia, primary, Herrero, Javier, primary, Ogunbiyi, Olagunju, primary, Gander, Amir, primary, Luong, Tu Vinh, primary, Thirlwell, Chrissie, primary, Caplin, Martyn, primary, Toumpanakis, Christos, primary, Peggs, Karl, primary, Quezada, Sergio A., primary, Marafioti, Teresa, primary, and Meyer, Tim, primary

Published
2023
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15. Supplementary Table from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, primary, Childs, Alexa, primary, Akarca, Ayse U., primary, Dhami, Pawan, primary, Vaikkinen, Heli, primary, Conde, Lucia, primary, Herrero, Javier, primary, Ogunbiyi, Olagunju, primary, Gander, Amir, primary, Luong, Tu Vinh, primary, Thirlwell, Chrissie, primary, Caplin, Martyn, primary, Toumpanakis, Christos, primary, Peggs, Karl, primary, Quezada, Sergio A., primary, Marafioti, Teresa, primary, and Meyer, Tim, primary

Published
2023
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16. Supplementary Data from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, primary, Childs, Alexa, primary, Akarca, Ayse U., primary, Dhami, Pawan, primary, Vaikkinen, Heli, primary, Conde, Lucia, primary, Herrero, Javier, primary, Ogunbiyi, Olagunju, primary, Gander, Amir, primary, Luong, Tu Vinh, primary, Thirlwell, Chrissie, primary, Caplin, Martyn, primary, Toumpanakis, Christos, primary, Peggs, Karl, primary, Quezada, Sergio A., primary, Marafioti, Teresa, primary, and Meyer, Tim, primary

Published
2023
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17. Body composition and lung cancer-associated cachexia in TRACERx

Author

Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C, Frankell, Alexander M, Watkins, Thomas BK, Martinez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Huebner, Ariana, Al Bakir, Maise, Sokac, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P, Christiani, David C, Mak, Raymond H, Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M, O'Rahilly, Stephen, Birkbak, Nicolai J, Aerts, Hugo JWL, Jamal-Hanjani, Mariam, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Van Loo, Peter, Szallasi, Zoltan, Kisistok, Judit, Diossy, Miklos, Demeulemeester, Jonas, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Abbosh, Christopher, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Hiley, Crispin T, Moore, David A, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Cadieux, Elizabeth Larose, Lim, Emilia L, Colliver, Emma, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Hartley, John A, Peggs, Karl S, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Grigoriadis, Kristiana, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Hill, Mark S, Dietzen, Michelle, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Pich, Oriol, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Zaccaria, Simone, Hessey, Sonya, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Male, Proteomics, Cachexia, Lung Neoplasms, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Body Weight, Body Composition, Humans, Neoplasm Recurrence, Local, Muscle, Skeletal, Neoplasm Proteins
Abstract

Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

18. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martinez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas BK, Pich, Oriol, Moore, David A, Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander, Bunkum, Abigail, Lim, Emilia L, Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T, Hill, Mark S, Cook, Daniel E, Wilson, Gareth A, Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R, Blackhall, Fiona H, Cave, Judith, Blyth, Kevin G, Nair, Arjun, Ahmed, Asia, Taylor, Magali N, Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Papadatos-Pastos, Dionysis, Forster, Martin D, Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio, Peggs, Karl S, Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Benafif, Sarah, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Krebs, Matthew G, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Puttick, Clare, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Black, James RM, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Clonal Evolution, Cohort Studies, Evolution, Molecular, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local, Clone Cells
Abstract

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

19. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M, Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L, Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S, Grigoriadis, Kristiana, Moore, David A, Black, James RM, Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas BK, Naceur-Lombardelli, Cristina, Cook, Daniel E, Salgado, Roberto, Wilson, Gareth A, Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martinez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G, Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Blyth, Kevin G, Fennell, Dean A, Forster, Martin D, Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J, Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G, Lester, Jason F, Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M, Lawrence, David, Navani, Neal, Janes, Sam M, Dive, Caroline, Blackhall, Fiona H, Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A, Peggs, Karl S, Schwarz, Roland F, Van Loo, Peter, Miedema, Daniel M, Birkbak, Nicolai J, Hiley, Crispin T, Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joa, Primrose, Lindsay, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Kaufmann, Tom L, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran L, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Rane, Jayant K, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Danson, Sarah, Robinson, Lily, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Lung Neoplasms, Treatment Outcome, DNA Copy Number Variations, Mutagenesis, Carcinoma, Non-Small-Cell Lung, Mutation, Smoking, Humans, Adenocarcinoma of Lung, Neoplasm Recurrence, Local, Phylogeny
Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

20. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A, Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Al Bakir, Maise, Watkins, Thomas BK, Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S, Frankell, Alexander M, Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L, Martinez-Ruiz, Carlos, Black, James RM, Biswas, Dhruva, Campbell, Brittany B, Lee, Claudia, Colliver, Emma, Enfield, Katey SS, Hessey, Sonya, Hiley, Crispin T, Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J, Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad R, Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R, Rekhtman, Natasha, Travis, William D, Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G, McGranahan, Nicholas, Swanton, Charles, Jamal-Hanjani, Mariam, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Castignani, Carla, Bailey, Chris, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Peggs, Karl S, Selvaraju, Kayalvizhi, Thol, Kerstin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Prymas, Paulina, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
TRACERx Consortium
Abstract

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

21. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles, Bosshard-Carter, Leticia, Goh, Gerald, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Horswell, Stuart, Bakir, Maise Al, Mitter, Richard, Escudero, Mickael, Xu, Hang, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Nye, Emma, Graca, Sofia, Joshi, Kroopa, Furness, Andrew, Ben Aissa, Assma, Wong, Yien Ning Sophia, Georgiou, Andy, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Taylor, Magali, Choudhary, Junaid, Califano, Raffaele, Taylor, Paul, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Moss, Stuart, Idries, Faiza, Bishop, Paul, Chaturvedi, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Rogan, Jane, Smith, Elaine, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Djearaman, Madava, Quesne, John Le, Thomas, Anne, Walter, Harriet, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Primrose, Lindsay, Amadi, Anita, Palmer, Shirley, Miller, Joy, Buchan, Keith, Edwards, Alison, Morgan, Fiona, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Dentro, Stefan, and Dessimoz, Christophe

Subjects
Lung cancer -- Genetic aspects -- Development and progression, DNA sequencing -- Methods, Phylogeny -- Observations, Cancer metastasis -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies., Author(s): Christopher Abbosh [1]; Nicolai J. Birkbak [1, 2]; Gareth A. Wilson [1, 2]; Mariam Jamal-Hanjani [1]; Tudor Constantin [3]; Raheleh Salari [3]; John Le Quesne [4]; David A. Moore [...]

Published
2017
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22. Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vaccinated and unvaccinated patients with cancer in Europe: results from the retrospective, multicentre, OnCovid registry study

Author

Pinato, David J, primary, Aguilar-Company, Juan, additional, Ferrante, Daniela, additional, Hanbury, Georgina, additional, Bower, Mark, additional, Salazar, Ramon, additional, Mirallas, Oriol, additional, Sureda, Anna, additional, Plaja, Andrea, additional, Cucurull, Marc, additional, Mesia, Ricard, additional, Townsend, Sarah, additional, Jackson, Amanda, additional, Dalla Pria, Alessia, additional, Newsom-Davis, Thomas, additional, Handford, Jasmine, additional, Sita-Lumsden, Ailsa, additional, Apthorp, Eleanor, additional, Vincenzi, Bruno, additional, Bertuzzi, Alexia, additional, Brunet, Joan, additional, Lambertini, Matteo, additional, Maluquer, Clara, additional, Pedrazzoli, Paolo, additional, Biello, Federica, additional, Sinclair, Alasdair, additional, Bawany, Samira, additional, Khalique, Saira, additional, Rossi, Sabrina, additional, Rogers, Lucy, additional, Murphy, Cian, additional, Belessiotis, Katherine, additional, Carmona-García, M Carmen, additional, Sharkey, Rachel, additional, García-Illescas, David, additional, Rizzo, Gianpiero, additional, Perachino, Marta, additional, Saoudi-Gonzalez, Nadia, additional, Doonga, Kris, additional, Fox, Laura, additional, Roldán, Elisa, additional, Gaidano, Gianluca, additional, Ruiz-Camps, Isabel, additional, Bruna, Riccardo, additional, Patriarca, Andrea, additional, Martinez-Vila, Clara, additional, Cantini, Luca, additional, Zambelli, Alberto, additional, Giusti, Raffaele, additional, Mazzoni, Francesca, additional, Caliman, Enrico, additional, Santoro, Armando, additional, Grosso, Federica, additional, Parisi, Alessandro, additional, Queirolo, Paola, additional, Aujayeb, Avinash, additional, Rimassa, Lorenza, additional, Prat, Aleix, additional, Tucci, Marco, additional, Libertini, Michela, additional, Grisanti, Salvatore, additional, Mukherjee, Uma, additional, Diamantis, Nikolaos, additional, Fusco, Vittorio, additional, Generali, Daniele, additional, Provenzano, Salvatore, additional, Gennari, Alessandra, additional, Tabernero, Josep, additional, Cortellini, Alessio, additional, Evans, Joanne S, additional, Swallow, Judith, additional, Chung, Chris, additional, Patel, Meera, additional, Dettorre, Gino, additional, Ottaviani, Diego, additional, Chowdhury, Amani, additional, Merry, Eve, additional, Chopra, Neha, additional, Lee, Alvin JX, additional, Sng, Christopher CT, additional, Yu, Tamara, additional, Shawe-Taylor, Marianne, additional, Bain, Hamish DC, additional, Wong, Yien Ning Sophia, additional, Galazi, Myria, additional, Benafif, Sarah, additional, Dileo, Palma, additional, Earnshaw, Irina, additional, Patel, Grisma, additional, Wu, Anjui, additional, Soosaipillai, Gehan, additional, Cooper, Lee, additional, Andaleeb, Ramis, additional, Dolly, Saoirse, additional, Srikandarajah, Krishnie, additional, Jones, Eleanor, additional, Van Hemelrijck, Mieke, additional, Moss, Charlotte, additional, Russell, Beth, additional, Chester, John, additional, Loizidou, Angela, additional, Piccart, Martine, additional, Cruz, Claudia A, additional, Reyes, Roxana, additional, Segui, Elia, additional, Marco-Hernández, Javier, additional, Viladot, Margarita, additional, Eremiev, Simeon, additional, Fort-Culillas, Roser, additional, Garcia, Isabel, additional, Liñan, Raquel, additional, Roqué Lloveras, Ariadna, additional, Harbeck, Nadia, additional, Wuerstlein, Rachel, additional, Henze, Franziska, additional, Mahner, Sven, additional, Felip, Eudald, additional, Pous, Anna, additional, D'Avanzo, Francesca, additional, Scotti, Lorenza, additional, Krengli, Marco, additional, Marrari, Andrea, additional, Delfanti, Sara, additional, Maconi, Antonio, additional, Betti, Marta, additional, Tonini, Giuseppe, additional, Di Fazio, Giuseppina Rita, additional, Tondini, Carlo, additional, Chiudinelli, Lorenzo, additional, Franchi, Michela, additional, Bertulli, Rossella, additional, Baggi, Alice, additional, Tovazzi, Valeria, additional, Ficorella, Corrado, additional, Porzio, Giampiero, additional, Saponara, Maristella, additional, Filetti, Marco, additional, Zoratto, Federica, additional, Paoloni, Francesco, additional, Berardi, Rossana, additional, Guida, Annalisa, additional, Bracarda, Sergio, additional, Iglesias, Maria, additional, Sanchez de Torre, Ana, additional, Tagliamento, Marco, additional, Colomba, Emeline, additional, and Pommeret, Fanny, additional

Published
2022
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23. Abstract 1591: Convergence of antigenic diversity and Tex-cell stability fatally constrains immune surveillance in non-small cell lung cancer (TRACERx) and HIV-1 infection (Protocol C)

Author

Reading, James L., primary, Rosenthal, Rachel, additional, Pich, Oriol, additional, Gamble, Samuel, additional, Ung, Seng Anakin, additional, Sahwangarrom, Teerapon, additional, Gration, Betty, additional, Wong, Yien Ning Sophia, additional, Black, Lucas, additional, Chain, Benny, additional, Hare, Jonathan, additional, Quezada, Sergio A., additional, and Swanton, Charles, additional

Published
2022
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24. Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, additional, Childs, Alexa, additional, Akarca, Ayse U., additional, Dhami, Pawan, additional, Vaikkinen, Heli, additional, Conde, Lucia, additional, Herrero, Javier, additional, Ogunbiyi, Olagunju, additional, Gander, Amir, additional, Luong, Tu Vinh, additional, Thirlwell, Chrissie, additional, Caplin, Martyn, additional, Toumpanakis, Christos, additional, Peggs, Karl, additional, Quezada, Sergio A., additional, Marafioti, Teresa, additional, and Meyer, Tim, additional

Published
2022
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25. Systemic Anti-Cancer Therapy and Metastatic Cancer Are Independent Mortality Risk Factors during Two UK Waves of the COVID-19 Pandemic at University College London Hospital

Author

Wong, Yien Ning Sophia, primary, Sng, Christopher C. T., additional, Ottaviani, Diego, additional, Patel, Grisma, additional, Chowdhury, Amani, additional, Earnshaw, Irina, additional, Sinclair, Alasdair, additional, Merry, Eve, additional, Wu, Anjui, additional, Galazi, Myria, additional, Benafif, Sarah, additional, Soosaipillai, Gehan, additional, Chopra, Neha, additional, Roylance, Rebecca, additional, Shaw, Heather, additional, and Lee, Alvin J. X., additional

Published
2021
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26. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study

Author

Pinato, David J, primary, Tabernero, Josep, additional, Bower, Mark, additional, Scotti, Lorenza, additional, Patel, Meera, additional, Colomba, Emeline, additional, Dolly, Saoirse, additional, Loizidou, Angela, additional, Chester, John, additional, Mukherjee, Uma, additional, Zambelli, Alberto, additional, Dalla Pria, Alessia, additional, Aguilar-Company, Juan, additional, Ottaviani, Diego, additional, Chowdhury, Amani, additional, Merry, Eve, additional, Salazar, Ramon, additional, Bertuzzi, Alexia, additional, Brunet, Joan, additional, Lambertini, Matteo, additional, Tagliamento, Marco, additional, Pous, Anna, additional, Sita-Lumsden, Ailsa, additional, Srikandarajah, Krishnie, additional, Colomba, Johann, additional, Pommeret, Fanny, additional, Seguí, Elia, additional, Generali, Daniele, additional, Grisanti, Salvatore, additional, Pedrazzoli, Paolo, additional, Rizzo, Gianpiero, additional, Libertini, Michela, additional, Moss, Charlotte, additional, Evans, Joanne S, additional, Russell, Beth, additional, Harbeck, Nadia, additional, Vincenzi, Bruno, additional, Biello, Federica, additional, Bertulli, Rossella, additional, Liñan, Raquel, additional, Rossi, Sabrina, additional, Carmona-García, Maria Carmen, additional, Tondini, Carlo, additional, Fox, Laura, additional, Baggi, Alice, additional, Fotia, Vittoria, additional, Parisi, Alessandro, additional, Porzio, Giampero, additional, Saponara, Maristella, additional, Cruz, Claudia Andrea, additional, García-Illescas, David, additional, Felip, Eudald, additional, Roqué Lloveras, Ariadna, additional, Sharkey, Rachel, additional, Roldán, Elisa, additional, Reyes, Roxana, additional, Earnshaw, Irina, additional, Ferrante, Daniela, additional, Marco-Hernández, Javier, additional, Ruiz-Camps, Isabel, additional, Gaidano, Gianluca, additional, Patriarca, Andrea, additional, Bruna, Riccardo, additional, Sureda, Anna, additional, Martinez-Vila, Clara, additional, Sanchez de Torre, Ana, additional, Cantini, Luca, additional, Filetti, Marco, additional, Rimassa, Lorenza, additional, Chiudinelli, Lorenzo, additional, Franchi, Michela, additional, Krengli, Marco, additional, Santoro, Armando, additional, Prat, Aleix, additional, Van Hemelrijck, Mieke, additional, Diamantis, Nikolaos, additional, Newsom-Davis, Thomas, additional, Gennari, Alessandra, additional, Cortellini, Alessio, additional, Swallow, Judith, additional, Chung, Chris, additional, Dettorre, Gino, additional, Chopra, Neha, additional, Lee, Alvin JX, additional, Sng, Christopher CT, additional, Wong, Yien Ning Sophia, additional, Galazi, Myria, additional, Benafif, Sarah, additional, Dileo, Palma, additional, Patel, Grisma, additional, Wu, Anjui, additional, Sinclair, Alasdair, additional, Soosaipillai, Gehan, additional, Jones, Eleanor, additional, Jackson, Amanda, additional, Piccart, Martine, additional, Colomba-Blameble, Emeline, additional, Cruz, Claudia A, additional, Segui, Elia, additional, Garcia Illescas, David, additional, Mirallas, Oriol, additional, Carbó, Anna, additional, Garcia, Isabel, additional, Wuerstlein, Rachel, additional, Mesia, Ricard, additional, Maluquer, Clara, additional, D'Avanzo, Francesca, additional, Tonini, Giuseppe, additional, Provenzano, Salvatore, additional, Tovazzi, Valeria, additional, Ficorella, Corrado, additional, Queirolo, Paola, additional, Giusti, Raffaele, additional, Mazzoni, Francesca, additional, Zoratto, Federica, additional, Tucci, Marco, additional, Berardi, Rossana, additional, Guida, Annalisa, additional, Bracarda, Sergio, additional, and Iglesias, Maria, additional

Published
2021
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27. Abstract LB004: Nivolumab (NIVO) and ipilimumab (IPI) treatment in prostate cancer with an immunogenic signature: cohort 1 of the NEPTUNES multi-centre, two-stage biomarker-selected Phase II trial

Author

Linch, Mark D., primary, Wong, Yien Ning Sophia, additional, Jones, Robert, additional, Sankey, Peter, additional, Josephs, Debra H., additional, Crabb, Simon J., additional, Staffurth, John, additional, Zarkar, Anjali, additional, White, Laura, additional, Duggan, Marian, additional, Pellizzari, Giulia, additional, Wheeler, Graham, additional, Beare, Sandy, additional, Cartwright, Hayley, additional, Linares, Josep, additional, Akarca, Ayse, additional, Quezada, Sergio A., additional, Ensell, Leah, additional, Hartley, John, additional, Attard, Gerhardt, additional, Burr, Joanna, additional, Jayaram, Anuradha, additional, Kularatne, Bihani, additional, Kayani, Mahaz, additional, Chung, Moon, additional, Pritchard, Colin C., additional, Freeman, Alex, additional, Haider, Aiman, additional, and Marafioti, Teresa, additional

Published
2021
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28. Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors

Author

Vargas, Frederick Arce, Furness, Andrew JS, Solomon, Isabelle, Joshi, Kroopa, Mekkaoui, Leila, Lesko, Marta H, Rota, Enrique Miranda, Dahan, Rony, Georgiou, Andrew, Sledzinska, Anna, Aissa, Assma Ben, Franz, Dafne, Sunderland, Mariana Werner, Wong, Yien Ning Sophia, Henry, Jake Y, O'Brien, Tim, Nicol, David, Challacombe, Ben, Beers, Stephen A, Consortium, Melanoma TRACERx, Consortium, Renal TRACERx, Consortium, Lung TRACERx, Turajlic, Samra, Gore, Martin, Larkin, James, Swanton, Charles, Chester, Kerry A, Pule, Martin, Ravetch, Jeffrey V, Marafioti, Teresa, Peggs, Karl S, and Quezada, Sergio A

Subjects
Model organisms, Chemical Biology & High Throughput, Signalling & Oncogenes, Human Biology & Physiology, Ecology,Evolution & Ethology, Genome Integrity & Repair, Gene Expression, hemic and immune systems, chemical and pharmacologic phenomena, Tumour Biology, Genetics & Genomics, Developmental Biology, Computational & Systems Biology
Abstract

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.

Published
2021
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29. Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: the OnCovid Inflammatory Score

Author

Dettorre, Gino M., Dolly, Saoirse, Loizidou, Angela, Chester, John, Jackson, Amanda, Mukherjee, Uma, Zambelli, Alberto, Aguilar Company, Juan, Bower, Mark, Sng, Christopher C. T., Salazar Soler, Ramón, Bertuzzi, Alexia, Brunet, Joan, Mesia, Ricard, Sita-Lumsden, Ailsa, Seguí, Elia, Biello, Federica, Generali, Daniele, Grisanti, Salvatore, Seeva, Pavetha, Rizzo, Gianpiero, Libertini, Michela, Maconi, Antonio, Moss, Charlotte, Russell, Beth, Harbeck, Nadia, Vincenzi, Bruno, Bertulli, Rossella, Ottaviani, Diego, Liñan, Raquel, Marrari, Andrea, Carmona García, M. Carmen, Chopra, Neha, Tondini, Carlo Alberto, Mirallas, Oriol, Tovazzi, Valeria, Fotia, Vittoria, Cruz, Claudia Andrea, Saoudi González, Nadia, Felip, Eudald, Roqué, Ariadna, Lee, Alvin J. X., Newsom-Davis, Tom, García Illescas, David, Reyes, Roxana, Wong, Yien Ning Sophia, Ferrante, Daniela, Scotti, Lorenza, Marco Hernández, Javier, Ruiz Camps, Isabel, Patriarca, Andrea, Rimassa, Lorenza, Chiudinelli, Lorenzo, Franchi, Michela, Santoro, Armando, Prat Aparicio, Aleix, Gennari, Alessandra, Van Hemelrijck, Mieke, Tabernero Caturla, Josep, Diamantis, Nikolaos, Pinato, David J., OnCovid study group, Dettorre, G. M., Dolly, S., Loizidou, A., Chester, J., Jackson, A., Mukherjee, U., Zambelli, A., Aguilar-Company, J., Bower, M., Sng, C. C. T., Salazar, R., Bertuzzi, A., Brunet, J., Mesia, R., Sita-Lumsden, A., Segui, E., Biello, F., Generali, D., Grisanti, S., Seeva, P., Rizzo, G., Libertini, M., Maconi, A., Moss, C., Russell, B., Harbeck, N., Vincenzi, B., Bertulli, R., Ottaviani, D., Linan, R., Marrari, A., Carmen Carmona-Garcia, M., Chopra, N., Tondini, C. A., Mirallas, O., Tovazzi, V., Fotia, V., Cruz, C. A., Saoudi-Gonzalez, N., Felip, E., Roque, A., Lee, A. J. X., Newsom-Davis, T., Garcia-Illescas, D., Reyes, R., Wong, Y. N. S., Ferrante, D., Scotti, L., Marco-Hernandez, J., Ruiz-Camps, I., Patriarca, A., Rimassa, L., Chiudinelli, L., Franchi, M., Santoro, A., Prat, A., Gennari, A., Van Hemelrijck, M., Tabernero, J., Diamantis, N., Pinato, D. J., Wellcome Trust, Institut Català de la Salut, [Dettorre GM] Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK. [Dolly S] Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust (GSTT), London, UK. [Loizidou A] Department of Infectious Diseases, Internal Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. [Chester J] Medical Oncology, School of Medicine, Cardiff University, Cardiff, UK. Medical Oncology, Velindre Cancer Centre, Cardiff, UK. [Jackson A] Clinical Trials, Velindre Cancer Centre, Cardiff, UK. [Mukherjee U] Medical Oncology, Barts Health NHS Trust, London, UK. [Aguilar-Company J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Mirallas O, Saoudi-Gonzalez N, García-Illescas D] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Ruiz-Camps I] Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Tabernero J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, Comorbidity, Systemic inflammation, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], COVID-19 Testing, 0302 clinical medicine, Neoplasms, Immunotherapy Biomarkers, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Immunology and Allergy, Medicine, Hypoalbuminemia, Young adult, Càncer, Multivariate Analysi, RC254-282, COVID-19 (Malaltia) - Complicacions, Cancer, Aged, 80 and over, OnCovid study group, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Middle Aged, Prognosis, Inflamació, Systemic Inflammatory Response Syndrome, 030220 oncology & carcinogenesis, Cohort, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation::Systemic Inflammatory Response Syndrome [DISEASES], Molecular Medicine, Female, medicine.symptom, Life Sciences & Biomedicine, Human, Adult, medicine.medical_specialty, Prognosi, Càncer - Epidemiologia, Immunology, neoplasias [ENFERMEDADES], inflammation mediator, Young Adult, 03 medical and health sciences, Internal medicine, Humans, afecciones patológicas, signos y síntomas::procesos patológicos::inflamación::síndrome de respuesta inflamatoria sistémica [ENFERMEDADES], Aged, Pharmacology, Science & Technology, business.industry, SARS-CoV-2, COVID-19, medicine.disease, inflammation, inflammation mediators, Blood Cell Count, Multivariate Analysis, Neoplasms [DISEASES], Systemic inflammatory response syndrome, 030104 developmental biology, Neoplasm, Lymphocytopenia, business, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Inflamació; Mediadors d'inflamació Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Inflamación; Mediadores de la inflamación Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Inflammation; Inflammation mediators Background Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p

Published
2021

31. Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: the OnCovid Inflammatory Score

Author

Dettorre, Gino M, primary, Dolly, Saoirse, additional, Loizidou, Angela, additional, Chester, John, additional, Jackson, Amanda, additional, Mukherjee, Uma, additional, Zambelli, Alberto, additional, Aguilar-Company, Juan, additional, Bower, Mark, additional, Sng, Christopher C T, additional, Salazar, Ramon, additional, Bertuzzi, Alexia, additional, Brunet, Joan, additional, Mesia, Ricard, additional, Sita-Lumsden, Ailsa, additional, Seguí, Elia, additional, Biello, Federica, additional, Generali, Daniele, additional, Grisanti, Salvatore, additional, Seeva, Pavetha, additional, Rizzo, Gianpiero, additional, Libertini, Michela, additional, Maconi, Antonio, additional, Moss, Charlotte, additional, Russell, Beth, additional, Harbeck, Nadia, additional, Vincenzi, Bruno, additional, Bertulli, Rossella, additional, Ottaviani, Diego, additional, Liñan, Raquel, additional, Marrari, Andrea, additional, Carmona-García, M Carmen, additional, Chopra, Neha, additional, Tondini, Carlo Alberto, additional, Mirallas, Oriol, additional, Tovazzi, Valeria, additional, Fotia, Vittoria, additional, Cruz, Claudia Andrea, additional, Saoudi-Gonzalez, Nadia, additional, Felip, Eudald, additional, Roqué, Ariadna, additional, Lee, Alvin J X, additional, Newsom-Davis, Tom, additional, García-Illescas, David, additional, Reyes, Roxana, additional, Wong, Yien Ning Sophia, additional, Ferrante, Daniela, additional, Scotti, Lorenza, additional, Marco-Hernández, Javier, additional, Ruiz-Camps, Isabel, additional, Patriarca, Andrea, additional, Rimassa, Lorenza, additional, Chiudinelli, Lorenzo, additional, Franchi, Michela, additional, Santoro, Armando, additional, Prat, Aleix, additional, Gennari, Alessandra, additional, Van Hemelrijck, Mieke, additional, Tabernero, Josep, additional, Diamantis, Nikolaos, additional, and Pinato, David J, additional

Published
2021
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32. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

Author

Lee, Lennard Y. W., Cazier, Jean-Baptiste, Starkey, Thomas, Briggs, Sarah E. W., Arnold, Roland, Bisht, Vartika, Booth, Stephen, Campton, Naomi A., Cheng, Vinton W. T., Collins, Graham, Curley, Helen M., Earwaker, Philip, Fittall, Matthew W., Gennatas, Spyridon, Goel, Anshita, Hartley, Simon, Hughes, Daniel J., Kerr, David, Lee, Alvin J. X., Lee, Rebecca J., Lee, Siow Ming, Mckenzie, Hayley, Middleton, Chris P., Murugaesu, Nirupa, Newsom-Davis, Tom, Olsson-Brown, Anna C., Palles, Claire, Powles, Thomas, Protheroe, Emily A., Purshouse, Karin, Sharma-Oates, Archana, Sivakumar, Shivan, Smith, Ashley J., Topping, Oliver, Turnbull, Chris D., Várnai, Csilla, Briggs, Adam D. M., Middleton, Gary, Kerr, Rachel, Gault, Abigail, Agnieszka, Michael, Bedair, Ahmed, Ghaus, Aisha, Akingboye, Akinfemi, Maynard, Alec, Pawsey, Alexander, Mohamed, Ali Abdulnabi, Okines, Alicia, Massey, Alison, Kwan, Amy, Ferreira, Ana, Angelakas, Angelos, Wu, Anjui, Tivey, Ann, Armstrong, Anne, Madhan, Annet, Pillai, Annet, Poon-King, Ashley, Kurec, Bartlomiej, Usborne, Caroline, Dobeson, Caroline, Thirlwell, Christina, Mitchell, Christian, Sng, Christopher, Scrase, Christopher, Jingree, Christopher, Brunner, Clair, Fuller, Claire, Griffin, Clare, Barrington, Craig, Muller, Daniel, Ottaviani, Diego, Gilbert, Duncan, Tacconi, Eliana, Copson, Ellen, Renninson, Emily, Cattell, Emma, Burke, Emma, Smith, Fiona, Holt, Francesca, Soosaipillai, Gehan, Boyce, Hayley, Shaw, Heather, Hollis, Helen, Bowyer, Helen, Anil, Iris, Illingworth, Jack, Gibson, Jack, Bhosle, Jaishree, Best, James, Barrett, Jane, Noble, Jillian, Sacco, Joseph, Chacko, Joseph, Chackathayil, Julia, Banfill, Kathryn, Feeney, Laura, Horsley, Laura, Cammaert, Lauren, Mukherjee, Leena, Eastlake, Leonie, Devereaux, Louise, Melcher, Lucinda, Cook, Lucy, Teng, Mabel, Hewish, Madeleine, Bhattacharyya, Madhumita, Choudhury, Mahbuba, Baxter, Mark, Scott-Brown, Martin, Fittall, Matthew, Tilby, Michael, Rowe, Michael, Alihilali, Mohammed, Galazi, Myria, Yousaf, Nadia, Chopra, Neha, Cox, Nicola, Chan, Olivia, Sheikh, Omar, Ramage, Paul, Greaves, Paul, Leonard, Pauline, Hall, Peter S., Naksukpaiboon, Piangfan, Corrie, Pippa, Peck, Rahul, Sharkey, Rachel, Bolton, Rachel, Sargent, Rebecca, Jyothirmayi, Rema, Goldstein, Robert, Oakes, Roderick, Shotton, Rohan, Kanani, Ruhi, Board, Ruth, Pettengell, Ruth, Claydon, Ryan, Moody, Sam, Massalha, Samah, Kathirgamakarthigeyan, Sangary, Dolly, Saoirse, Derby, Sarah, Lowndes, Sarah, Benafif, Sarah, Eeckelaers, Sarah, Kingdon, Sarah, Ayers, Sarah, Brown, Sean, Ellis, Shawn, Parikh, Shefali, Pugh, Sian, Shamas, Simon, Wyatt, Simon, Grumett, Simon, Lau, Sin, Wong, Yien Ning Sophia, McGrath, Sophie, Cornthwaite, Stephanie, Hibbs, Stephen, Tillet, Tania, Rabbi, Taslima, Robinson, Tim, Roques, Tom, Angelis, Vasileios, Woodcock, Victoria, Brown, Victoria, Peng, YingYing, Drew, Yvette, Hudson, Zoe, and HASH(0x5651ca095ff8)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Pneumonia, Viral, Population, Risk Assessment, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Neoplasms, Internal medicine, Correspondence, Epidemiology, medicine, Humans, Prospective Studies, Lung cancer, education, Prospective cohort study, Pandemics, Aged, Cause of death, Aged, 80 and over, education.field_of_study, Manchester Cancer Research Centre, SARS-CoV-2, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, COVID-19, Cancer, Odds ratio, Middle Aged, medicine.disease, Hospitalization, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, Coronavirus Infections, business, RA
Abstract

BACKGROUND: Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK. METHODS: We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case-fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models. FINDINGS: 319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case-fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40-49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio [OR] 1·57, 95% CI 1·15-2·15; p

Published
2020
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33. Presenting features and early mortality from SARS-CoV-2 infection in cancer patients during the initial stage of the COVID-19 pandemic in Europe

Author

Pinato, David J., Lee, Alvin J.X., Biello, Federica, Seguí, Elia, Aguilar-Company, Juan, Carbó, Anna, Bruna, Riccardo, Bower, Mark, Rizzo, Gianpiero, Benafif, Sarah, Carmona, Carme, Chopra, Neha, Cruz, Claudia Andrea, D'avanzo, Francesca, Evans, Joanne S., Galazi, Myria, Garcia-Fructuoso, Isabel, Pria, Alessia D., Newsom-Davis, Thomas, Ottaviani, Diego, Patriarca, Andrea, Reyes, Roxana, Sharkey, Rachel, Sng, Christopher C.T., Wong, Yien Ning Sophia, Ferrante, Daniela, Scotti, Lorenza, Avanzi, Gian Carlo, Bellan, Mattia, Castello, Luigi Mario, Marco-Hernández, Javier, Mollà, Meritxell, Pirisi, Mario, Ruiz-Camps, Isabel, Sainaghi, Pier Paolo, Gaidano, Gianluca, Brunet, Joan, Tabernero, Josep, Prat, Aleix, Gennari, Alessandra, Universitat Autònoma de Barcelona, Pinato, David J., Lee, Alvin J.X., Biello, Federica, Seguí, Elia, Aguilar-Company, Juan, Carbó, Anna, Bruna, Riccardo, Bower, Mark, Rizzo, Gianpiero, Benafif, Sarah, Carmona, Carme, Chopra, Neha, Cruz, Claudia Andrea, D'avanzo, Francesca, Evans, Joanne S., Galazi, Myria, Garcia-Fructuoso, Isabel, Pria, Alessia D., Newsom-Davis, Thomas, Ottaviani, Diego, Patriarca, Andrea, Reyes, Roxana, Sharkey, Rachel, Sng, Christopher C.T., Wong, Yien Ning Sophia, Ferrante, Daniela, Scotti, Lorenza, Avanzi, Gian Carlo, Bellan, Mattia, Castello, Luigi Mario, Marco-Hernández, Javier, Mollà, Meritxell, Pirisi, Mario, Ruiz-Camps, Isabel, Sainaghi, Pier Paolo, Gaidano, Gianluca, Brunet, Joan, Tabernero, Josep, Prat, Aleix, Gennari, Alessandra, and Universitat Autònoma de Barcelona

Abstract

Funding: D.J.P. is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416) and acknowledges grant support by the Cancer Treatment and Research Trust (CTRT) as well as infrastructural support by the Cancer Research UK Imperial Centre. GG is supported by the AIRC 5 × 1000 Grant, No. 21198, Associazione Italiana per la Ricerca sul Cancro Foundation, Milan, Italy. A.G. is supported by the AIRC IG grant, No. 14230, Associazione Italiana per la Ricerca sul Cancro Foundation, Milan, Italy. A.G., G.G., G.C.A., L.M.C., M.B., P.P.S., M.P. from the University of Piemonte Orientale acknowledge support from the UPO Aging Project., We describe the outcomes in cancer patients during the initial outbreak of the COVID-19 in Europe from the retrospective, multi-center observational OnCovid study. We identified 204 cancer patients from eight centers in the United Kingdom, Italy, and Spain aged > 18 (mean = 69) and diagnosed with COVID-19 between February 26th and April 1st, 2020. A total of 127 (62%) were male, 184 (91%) had a diagnosis of solid malignancy, and 103 (51%) had non-metastatic disease. A total of 161 (79%) had > 1 co-morbidity. A total of 141 (69%) patients had > 1 COVID-19 complication. A total of 36 (19%) were escalated to high-dependency or intensive care. A total of 59 (29%) died, 53 (26%) were discharged, and 92 (45%) were in-hospital survivors. Mortality was higher in patients aged > 65 (36% versus 16%), in those with > 2 co-morbidities (40% versus 18%) and developing > 1 complication from COVID-19 (38% versus 4%, p = 0.004). Multi-variable analyses confirmed age > 65 and > 2 co-morbidities to predict for patient mortality independent of tumor stage, active malignancy, or anticancer therapy. During the early outbreak of SARS-CoV-2 infection in Europe co-morbid burden and advancing age predicted for adverse disease course in cancer patients. The ongoing OnCovid study will allow us to compare risks and outcomes in cancer patients between the initial and later stages of the COVID-19 pandemic.

Published
2020

34. Specialist palliative and end-of-life care for patients with cancer and SARS-CoV-2 infection: a European perspective

Author

Soosaipillai, Gehan, primary, Wu, Anjui, additional, Dettorre, Gino M, additional, Diamantis, Nikolaos, additional, Chester, John, additional, Moss, Charlotte, additional, Aguilar-Company, Juan, additional, Bower, Mark, additional, Sng, Christopher CT, additional, Salazar, Ramon, additional, Brunet, Joan, additional, Jones, Eleanor, additional, Mesia, Ricard, additional, Jackson, Amanda, additional, Mukherjee, Uma, additional, Sita-Lumsden, Ailsa, additional, Seguí, Elia, additional, Ottaviani, Diego, additional, Carbó, Anna, additional, Benafif, Sarah, additional, Würstlein, Rachel, additional, Carmona, Carme, additional, Chopra, Neha, additional, Cruz, Claudia Andrea, additional, Swallow, Judith, additional, Saoudi, Nadia, additional, Felip, Eudald, additional, Galazi, Myria, additional, Garcia-Fructuoso, Isabel, additional, Lee, Alvin J. X., additional, Newsom-Davis, Thomas, additional, Wong, Yien Ning Sophia, additional, Sureda, Anna, additional, Maluquer, Clara, additional, Ruiz-Camps, Isabel, additional, Cabirta, Alba, additional, Prat, Aleix, additional, Loizidou, Angela, additional, Gennari, Alessandra, additional, Ferrante, Daniela, additional, Tabernero, Josep, additional, Russell, Beth, additional, Van Hemelrijck, Mieke, additional, Dolly, Saoirse, additional, Hulbert-Williams, Nicholas J, additional, Pinato, David J, additional, Mollà, Meritxell, additional, Reyes, Roxana, additional, Marco-Hernández, Javier, additional, Bruna, Riccardo, additional, Biello, Federica, additional, Patriarca, Andrea, additional, Zambelli, Alberto, additional, Tondini, Carlo, additional, Fotia, Vittoria, additional, Chiudinelli, Lorenzo, additional, Franchi, Michela, additional, Generali, Daniele, additional, Grisanti, Salvatore, additional, Tovazzi, Valeria, additional, Bertuzzi, Alexia, additional, Marrari, Andrea, additional, Seeva, Pavetha, additional, Dileo, Palma, additional, Rizzo, Gianpiero, additional, Libertini, Michela, additional, Maconi, Antonio, additional, Betti, Marta, additional, Provenzano, Salvatore, additional, Harbeck, Nadia, additional, Vincenzi, Bruno, additional, Bertulli, Rossella, additional, Liñan, Raquel, additional, Roqué, Ariadna, additional, Mirallas, Oriol, additional, García-Illescas, David, additional, Scotti, Lorenza, additional, Dalla Pria, Alessia, additional, D’Avanzo, Francesca, additional, Martinez, Maria, additional, Evans, Joanne S, additional, Sharkey, Rachel, additional, Rimassa, Lorenza, additional, Santoro, Armando, additional, Gaidano, Gianluca, additional, and Izuzquiza, Macarena, additional

Published
2021
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35. Cancer History and Systemic Anti-Cancer Therapy Independently Predict COVID-19 Mortality: A UK Tertiary Hospital Experience

Author

Sng, Christopher C. T., primary, Wong, Yien Ning Sophia, additional, Wu, Anjui, additional, Ottaviani, Diego, additional, Chopra, Neha, additional, Galazi, Myria, additional, Benafif, Sarah, additional, Soosaipillai, Gehan, additional, Roylance, Rebecca, additional, Lee, Alvin J. X., additional, and Shaw, Heather, additional

Published
2020
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36. Clinical Portrait of the SARS-CoV-2 Epidemic in European Patients with Cancer

Author

Pinato, David J., primary, Zambelli, Alberto, additional, Aguilar-Company, Juan, additional, Bower, Mark, additional, Sng, Christopher C.T., additional, Salazar, Ramon, additional, Bertuzzi, Alexia, additional, Brunet, Joan, additional, Mesia, Ricard, additional, Seguí, Elia, additional, Biello, Federica, additional, Generali, Daniele, additional, Grisanti, Salvatore, additional, Rizzo, Gianpiero, additional, Libertini, Michela, additional, Maconi, Antonio, additional, Harbeck, Nadia, additional, Vincenzi, Bruno, additional, Bertulli, Rossella, additional, Ottaviani, Diego, additional, Carbó, Anna, additional, Bruna, Riccardo, additional, Benafif, Sarah, additional, Marrari, Andrea, additional, Wuerstlein, Rachel, additional, Carmona-Garcia, M. Carmen, additional, Chopra, Neha, additional, Tondini, Carlo, additional, Mirallas, Oriol, additional, Tovazzi, Valeria, additional, Betti, Marta, additional, Provenzano, Salvatore, additional, Fotia, Vittoria, additional, Cruz, Claudia Andrea, additional, Dalla Pria, Alessia, additional, D'Avanzo, Francesca, additional, Evans, Joanne S., additional, Saoudi-Gonzalez, Nadia, additional, Felip, Eudald, additional, Galazi, Myria, additional, Garcia-Fructuoso, Isabel, additional, Lee, Alvin J.X., additional, Newsom-Davis, Thomas, additional, Patriarca, Andrea, additional, García-Illescas, David, additional, Reyes, Roxana, additional, Dileo, Palma, additional, Sharkey, Rachel, additional, Wong, Yien Ning Sophia, additional, Ferrante, Daniela, additional, Marco-Hernández, Javier, additional, Sureda, Anna, additional, Maluquer, Clara, additional, Ruiz-Camps, Isabel, additional, Gaidano, Gianluca, additional, Rimassa, Lorenza, additional, Chiudinelli, Lorenzo, additional, Izuzquiza, Macarena, additional, Cabirta, Alba, additional, Franchi, Michela, additional, Santoro, Armando, additional, Prat, Aleix, additional, Tabernero, Josep, additional, Gennari, Alessandra, additional, Avanzi, Gian Carlo, additional, Bellan, Mattia, additional, Castello, Luigi Mario, additional, Martinez, Maria, additional, Mollà, Meritxell, additional, Pirisi, Mario, additional, Scotti, Lorenza, additional, and Swallow, Judith, additional

Published
2020
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37. Presenting Features and Early Mortality from SARS-CoV-2 Infection in Cancer Patients during the Initial Stage of the COVID-19 Pandemic in Europe

Author

Pinato, David J., primary, Lee, Alvin J. X., additional, Biello, Federica, additional, Seguí, Elia, additional, Aguilar-Company, Juan, additional, Carbó, Anna, additional, Bruna, Riccardo, additional, Bower, Mark, additional, Rizzo, Gianpiero, additional, Benafif, Sarah, additional, Carmona, Carme, additional, Chopra, Neha, additional, Cruz, Claudia Andrea, additional, D’Avanzo, Francesca, additional, Evans, Joanne S., additional, Galazi, Myria, additional, Garcia-Fructuoso, Isabel, additional, Dalla Pria, Alessia, additional, Newsom-Davis, Thomas, additional, Ottaviani, Diego, additional, Patriarca, Andrea, additional, Reyes, Roxana, additional, Sharkey, Rachel, additional, Sng, Christopher C. T., additional, Wong, Yien Ning Sophia, additional, Ferrante, Daniela, additional, Scotti, Lorenza, additional, Avanzi, Gian Carlo, additional, Bellan, Mattia, additional, Castello, Luigi Mario, additional, Marco-Hernández, Javier, additional, Mollà, Meritxell, additional, Pirisi, Mario, additional, Ruiz-Camps, Isabel, additional, Sainaghi, Pier Paolo, additional, Gaidano, Gianluca, additional, Brunet, Joan, additional, Tabernero, Josep, additional, Prat, Aleix, additional, and Gennari, Alessandra, additional

Published
2020
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38. Intratumoural (IT) evolutionary landscape of high-risk prostate cancer and outcome: The PROGENY (PROstate cancer GENomic heterogeneitY) study of genomic and immune parameters.

Author

Jayaram, Anuradha, primary, Goh, Gerald, additional, Kularatne, Bihani Yoshana, additional, Waterhouse, Jasmin, additional, Shanmugabavan, Yaalini, additional, Rowan, Andrew, additional, Wong, Yien Ning Sophia, additional, Freeman, Alex, additional, Akarca, Ayse, additional, Herrero, Javier, additional, Rosenthal, Rachel, additional, McGranahan, Nicholas, additional, Hung, Michelle, additional, Emberton, Mark, additional, Attard, Gerhardt, additional, Quezada, Sergio A., additional, Marafioti, Teresa, additional, Ahmed, Hashim Uddin, additional, Swanton, Charles, additional, and Linch, Mark David, additional

Published
2020
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39. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer

Author

Joshi, Kroopa, Robert de Massy, Marc, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, Hatipoglu, Emine, Oakes, Theres, Rosenthal, Rachel, Peacock, Thomas, Ronel, Tahel, Noursadeghi, Mahdad, Turati, Virginia, Georgiou, Andrew, Furness, Andrew J. S., Wong, Yien Ning Sophia, Ben Aissa, Assma, Werner Sunderland, Mariana, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai Juul, Wilson, Gareth A., Hiley, Crispin T, Ghorani, Ehsan, Guerra-Assunção, José Afonso, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S, McGranahan, Nicholas, Swanton, Charles, Quezada, Sergio A., Chain, Benny, Joshi, Kroopa, Robert de Massy, Marc, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, Hatipoglu, Emine, Oakes, Theres, Rosenthal, Rachel, Peacock, Thomas, Ronel, Tahel, Noursadeghi, Mahdad, Turati, Virginia, Georgiou, Andrew, Furness, Andrew J. S., Wong, Yien Ning Sophia, Ben Aissa, Assma, Werner Sunderland, Mariana, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai Juul, Wilson, Gareth A., Hiley, Crispin T, Ghorani, Ehsan, Guerra-Assunção, José Afonso, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S, McGranahan, Nicholas, Swanton, Charles, Quezada, Sergio A., and Chain, Benny

Abstract

Somatic mutations together with immunoediting drive extensive heterogeneity within non-small-cell lung cancer (NSCLC). Herein we examine heterogeneity of the T cell antigen receptor (TCR) repertoire. The number of TCR sequences selectively expanded in tumors varies within and between tumors and correlates with the number of nonsynonymous mutations. Expanded TCRs can be subdivided into TCRs found in all tumor regions (ubiquitous) and those present in a subset of regions (regional). The number of ubiquitous and regional TCRs correlates with the number of ubiquitous and regional nonsynonymous mutations, respectively. Expanded TCRs form part of clusters of TCRs of similar sequence, suggestive of a spatially constrained antigen-driven process. CD8+ tumor-infiltrating lymphocytes harboring ubiquitous TCRs display a dysfunctional tissue-resident phenotype. Ubiquitous TCRs are preferentially detected in the blood at the time of tumor resection as compared to routine follow-up. These findings highlight a noninvasive method to identify and track relevant tumor-reactive TCRs for use in adoptive T cell immunotherapy.

Published
2019

40. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies

Author

Arce Vargas, Frederick, Furness, Andrew J.S., Litchfield, Kevin, Joshi, Kroopa, Rosenthal, Rachel, Ghorani, Ehsan, Solomon, Isabelle, Lesko, Marta H., Ruef, Nora, Roddie, Claire, Henry, Jake Y., Spain, Lavinia, Ben Aissa, Assma, Georgiou, Andrew, Wong, Yien Ning Sophia, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Nicol, David, O'Brien, Tim, Mårtensson, Linda, Ljungars, Anne, Teige, Ingrid, Frendéus, Björn, Pule, Martin, Marafioti, Teresa, Gore, Martin, Larkin, James, Turajlic, Samra, Swanton, Charles, Peggs, Karl S., Quezada, Sergio A., Harrington, Kevin, Melcher, Alan, Wotherspoon, Andrew, Francis, Nicholas, Challacombe, Ben, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Lynch, Joanna, Rudman, Sarah, Chowdhury, Simon, Harrison-Phipps, Karen, Varia, Mary, Horsfield, Catherine, Polson, Alexander, Stamp, Gordon, O'Donnell, Marie, Drake, William, Hill, Peter, Hrouda, David, Mayer, Eric, Olsburgh, Jonathan, Kooiman, Gordon, O'Connor, Kevin, Stewart, Grant, Aitchison, Michael, Tran, Maxine, Fotiadis, Nicos, Verma, Hema, Lopez, Jose, Lester, Jason, Morgan, Fiona, Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Fennell, Dean, Shaw, Jacqui, Le Quesne, John, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lock, Sara, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Novasio, Juliette, Joseph, Leena, Bishop, Paul, Chaturvedi, Anshuman, Marie Quinn, Anne, Doran, Helen, leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Brady, Ged, Rothwell, Dominic, Gulati, Sakshi, Chemie, Francesca, Tugwood, Jonathan, Pierce, Jackie, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, George, Robert, Patrini, Davide, Falzon, Mary, Borg, Elaine, Khiroya, Reena, Jamal-Hanjani, Mariam, Wilson, Gareth, Juul Birkbak, Nicolai, Watkins, Thomas, McGranahan, Nicholas, Abbosh, Christopher, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Rowan, Andrew, Hiley, Crispin, Goldman, Jacki, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Shaw, Penny, Veeriah, Raju, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Hynds, Robert, Werner Sunderland, Mariana, Reading, James, Novelli, Marco, Oukrif, Dahmane, Janes, Sam, Forster, Martin, Ahmad, Tanya, Ming Lee, Siow, van Loo, Peter, Herrero, Javier, Hartley, John, Kevin Stone, Richard, Denner, Tamara, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Ward, Sophie, Elgar, Greg, Al-Bakir, Maise, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Papadatos-Pastos, Dionysis, Scarci, Marco, Gorman, Pat, Lowe, Helen, Ensell, Leah, Moore, David, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Tavares Barbosa, Monica, Nicholson, Andrew, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Elena Cufari, Maria, Carlo Ronquillo, John, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Prakash, Vineet, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Russell, Peter, Light, Teresa, Horey, Tracey, Blyth, Kevin, Dick, Craig, and Kirk, Alan

Abstract

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

Published
2018

41. Nivolumab and ipilimumab treatment in prostate cancer with an immunogenic signature (NEPTUNES).

Author

Wong, Yien Ning Sophia, primary, Sankey, Peter, additional, Josephs, Debra Hannah, additional, Jones, Robert J, additional, Crabb, Simon J., additional, Beare, Sandy, additional, Duggan, Marian, additional, White, Laura, additional, Charlaftis, Nikolaos, additional, Wheeler, Graham, additional, Linares, Josep, additional, Quezada, Sergio A., additional, Ensell, Leah, additional, Flanagan, Cliona, additional, Kularatne, Bihani Yoshana, additional, Chung, Moon, additional, Pritchard, Colin C., additional, Freeman, Alex, additional, Marafioti, Teresa, additional, and Linch, Mark David, additional

Published
2019
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42. Fc-Optimized Anti-CD25 depletes tumor-infiltrating regulatory T Cells and synergizes with PD-1 Blockade to eradicate established tumors

Author

Arce Vargas, Frederick, Furness, Andrew J.S., Solomon, Isabelle, Joshi, Kroopa, Mekkaoui, Leila, Lesko, Marta H., Miranda Rota, Enrique, Dahan, Rony, Georgiou, Andrew, Sledzinska, Anna, Ben Aissa, Assma, Franz, Dafne, Werner Sunderland, Mariana, Wong, Yien Ning Sophia, Henry, Jake Y., O’Brien, Tim, Nicol, David, Challacombe, Ben, Beers, Stephen A., Turajlic, Samra, Gore, Martin, Larkin, James, Swanton, Charles, Chester, Kerry A., Pule, Martin, Ravetch, Jeffrey V., Marafioti, Teresa, Peggs, Karl S., Quezada, Sergio A., Spain, Lavinia, Wotherspoon, Andrew, Francis, Nicholas, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Soultati, Aspasia, Stares, Mark, Lynch, Joanna, Fotiadis, Nicos, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Rudman, Sarah, Chowdhury, Simon, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Shafi, Seema, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Bosshard-Carter, Leticia, Goh, Gerald, Rosenthal, Rachel, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Wilson, Gareth, Birkbak, Nicolai J., Watkins, Thomas B.K., McGranahan, Nicholas, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Van Loo, Peter, Rowan, Andrew, Xu, Hang, Hiley, Crispin, Abbosh, Christopher, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Matthews, Nik, Elgar, Greg, Ward, Sophia, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Graca, Sofia, Al Bakir, Maise, Hartley, John A., Lowe, Helen L., Herrero, Javier, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, Kolvekar, Shyam, Falzon, Mary, Borg, Elaine, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Oukrif, Dahmane, Janes, Sam M., Thakrar, Ricky, Forster, Martin, Ahmad, Tanya, Lee, Siow Ming, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Joseph, Leena, Bishop, Paul, Chaturved, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Fennell, Dean, Shaw, Jacqui A., Le Quesne, John, Moore, David, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Amadi, Anita, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lester, Jason, Edwards, Alison, Morgan, Fiona, Adams, Haydn, Davies, Helen, Kornaszewska, Malgorzata, Attanoos, Richard, Lock, Sara, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Iles, Natasha, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jorda, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Ismail, Babikir, Irvin-sellers, Melanie, Prakash, Vineet, Russell, Peter, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, and Asante-Siaw, Julius

Subjects
hemic and immune systems, chemical and pharmacologic phenomena, R1
Abstract

Summary\ud \ud CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.

Published
2017

43. Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment

Author

Wong, Yien Ning Sophia, primary, Joshi, Kroopa, additional, Khetrapal, Pramit, additional, Ismail, Mazlina, additional, Reading, James L., additional, Sunderland, Mariana Werner, additional, Georgiou, Andrew, additional, Furness, Andrew J.S., additional, Ben Aissa, Assma, additional, Ghorani, Ehsan, additional, Oakes, Theres, additional, Uddin, Imran, additional, Tan, Wei Shen, additional, Feber, Andrew, additional, McGovern, Ursula, additional, Swanton, Charles, additional, Freeman, Alex, additional, Marafioti, Teresa, additional, Briggs, Timothy P., additional, Kelly, John D., additional, Powles, Thomas, additional, Peggs, Karl S., additional, Chain, Benjamin M., additional, Linch, Mark D., additional, and Quezada, Sergio A., additional

Published
2018
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44. Characterisation of the TCR repertoire in NSCLC to reveal the relationship between TCR heterogeneity and genetic heterogeneity that is influenced by mutational load and is associated with disease recurrence.

Author

Joshi, Kroopa, primary, Ismail, Mazlina, additional, Reading, James L, additional, Robert De Massy, Marc, additional, Uddin, Imran, additional, Jamal-Hanjani, Mariam, additional, Veeriah, Selvaraju, additional, Oakes, Theres, additional, Wong, Yien Ning Sophia, additional, Furness, Andrew James Scott, additional, Ghorani, Ehsan, additional, Georgiou, Andrew, additional, Beastall, Carmella, additional, Mangal, Nagina, additional, Ben Aissa, Assma, additional, Werner Sunderland, Mariana, additional, Peggs, Karl, additional, Swanton, Charles, additional, Chain, Benjamin, additional, and Quezada, Sergio A, additional

Published
2018
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45. Systematic evaluation of the immune microenvironment of neuroendocrine tumours

Author

Vesely, Clare, primary, Childs, Alexa, additional, Wong, Yien Ning Sophia, additional, Ogunbiyi, Olagunju, additional, Gander, Amir, additional, Luong, Tu Vinh, additional, Thirlwell, Chrissie, additional, Caplin, Martyn, additional, Peggs, Karl, additional, Marafioti, Teresa, additional, Quezada, Sergio A., additional, and Meyer, Tim, additional

Published
2017
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46. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Author

McGranahan, Nicholas, primary, Rosenthal, Rachel, additional, Hiley, Crispin T., additional, Rowan, Andrew J., additional, Watkins, Thomas B.K., additional, Wilson, Gareth A., additional, Birkbak, Nicolai J., additional, Veeriah, Selvaraju, additional, Van Loo, Peter, additional, Herrero, Javier, additional, Swanton, Charles, additional, Jamal-Hanjani, Mariam, additional, Shafi, Seema, additional, Czyzewska-Khan, Justyna, additional, Johnson, Diana, additional, Laycock, Joanne, additional, Bosshard-Carter, Leticia, additional, Gorman, Pat, additional, Hynds, Robert E., additional, Wilson, Gareth, additional, McGranahan, Nicholas, additional, Horswell, Stuart, additional, Mitter, Richard, additional, Escudero, Mickael, additional, Stewart, Aengus, additional, Rowan, Andrew, additional, Xu, Hang, additional, Turajlic, Samra, additional, Hiley, Crispin, additional, Abbosh, Christopher, additional, Goldman, Jacki, additional, Stone, Richard Kevin, additional, Denner, Tamara, additional, Matthews, Nik, additional, Elgar, Greg, additional, Ward, Sophia, additional, Costa, Marta, additional, Begum, Sharmin, additional, Phillimore, Ben, additional, Chambers, Tim, additional, Nye, Emma, additional, Graca, Sofia, additional, Al Bakir, Maise, additional, Joshi, Kroopa, additional, Furness, Andrew, additional, Ben Aissa, Assma, additional, Wong, Yien Ning Sophia, additional, Georgiou, Andy, additional, Quezada, Sergio, additional, Hartley, John A., additional, Lowe, Helen L., additional, Lawrence, David, additional, Hayward, Martin, additional, Panagiotopoulos, Nikolaos, additional, Kolvekar, Shyam, additional, Falzon, Mary, additional, Borg, Elaine, additional, Marafioti, Teresa, additional, Simeon, Celia, additional, Hector, Gemma, additional, Smith, Amy, additional, Aranda, Marie, additional, Novelli, Marco, additional, Oukrif, Dahmane, additional, Janes, Sam M., additional, Thakrar, Ricky, additional, Forster, Martin, additional, Ahmad, Tanya, additional, Lee, Siow Ming, additional, Papadatos-Pastos, Dionysis, additional, Carnell, Dawn, additional, Mendes, Ruheena, additional, George, Jeremy, additional, Navani, Neal, additional, Ahmed, Asia, additional, Taylor, Magali, additional, Choudhary, Junaid, additional, Summers, Yvonne, additional, Califano, Raffaele, additional, Taylor, Paul, additional, Shah, Rajesh, additional, Krysiak, Piotr, additional, Rammohan, Kendadai, additional, Fontaine, Eustace, additional, Booton, Richard, additional, Evison, Matthew, additional, Crosbie, Phil, additional, Moss, Stuart, additional, Idries, Faiza, additional, Joseph, Leena, additional, Bishop, Paul, additional, Chaturved, Anshuman, additional, Quinn, Anne Marie, additional, Doran, Helen, additional, Leek, Angela, additional, Harrison, Phil, additional, Moore, Katrina, additional, Waddington, Rachael, additional, Novasio, Juliette, additional, Blackhall, Fiona, additional, Rogan, Jane, additional, Smith, Elaine, additional, Dive, Caroline, additional, Tugwood, Jonathan, additional, Brady, Ged, additional, Rothwell, Dominic G., additional, Chemi, Francesca, additional, Pierce, Jackie, additional, Gulati, Sakshi, additional, Naidu, Babu, additional, Langman, Gerald, additional, Trotter, Simon, additional, Bellamy, Mary, additional, Bancroft, Hollie, additional, Kerr, Amy, additional, Kadiri, Salma, additional, Webb, Joanne, additional, Middleton, Gary, additional, Djearaman, Madava, additional, Fennell, Dean, additional, Shaw, Jacqui A., additional, Le Quesne, John, additional, Moore, David, additional, Nakas, Apostolos, additional, Rathinam, Sridhar, additional, Monteiro, William, additional, Marshall, Hilary, additional, Nelson, Louise, additional, Bennett, Jonathan, additional, Riley, Joan, additional, Primrose, Lindsay, additional, Martinson, Luke, additional, Anand, Girija, additional, Khan, Sajid, additional, Amadi, Anita, additional, Nicolson, Marianne, additional, Kerr, Keith, additional, Palmer, Shirley, additional, Remmen, Hardy, additional, Miller, Joy, additional, Buchan, Keith, additional, Chetty, Mahendran, additional, Gomersall, Lesley, additional, Lester, Jason, additional, Edwards, Alison, additional, Morgan, Fiona, additional, Adams, Haydn, additional, Davies, Helen, additional, Kornaszewska, Malgorzata, additional, Attanoos, Richard, additional, Lock, Sara, additional, Verjee, Azmina, additional, MacKenzie, Mairead, additional, Wilcox, Maggie, additional, Bell, Harriet, additional, Hackshaw, Allan, additional, Ngai, Yenting, additional, Smith, Sean, additional, Gower, Nicole, additional, Ottensmeier, Christian, additional, Chee, Serena, additional, Johnson, Benjamin, additional, Alzetani, Aiman, additional, Shaw, Emily, additional, Lim, Eric, additional, De Sousa, Paulo, additional, Barbosa, Monica Tavares, additional, Bowman, Alex, additional, Jordan, Simon, additional, Rice, Alexandra, additional, Raubenheimer, Hilgardt, additional, Proli, Chiara, additional, Cufari, Maria Elena, additional, Ronquillo, John Carlo, additional, Kwayie, Angela, additional, Bhayani, Harshil, additional, Hamilton, Morag, additional, Bakar, Yusura, additional, Mensah, Natalie, additional, Ambrose, Lyn, additional, Devaraj, Anand, additional, Buderi, Silviu, additional, Finch, Jonathan, additional, Azcarate, Leire, additional, Chavan, Hema, additional, Green, Sophie, additional, Mashinga, Hillaria, additional, Nicholson, Andrew G., additional, Lau, Kelvin, additional, Sheaff, Michael, additional, Schmid, Peter, additional, Conibear, John, additional, Ezhil, Veni, additional, Ismail, Babikir, additional, Irvin-sellers, Melanie, additional, Prakash, Vineet, additional, Russell, Peter, additional, Light, Teresa, additional, Horey, Tracey, additional, Danson, Sarah, additional, Bury, Jonathan, additional, Edwards, John, additional, Hill, Jennifer, additional, Matthews, Sue, additional, Kitsanta, Yota, additional, Suvarna, Kim, additional, Fisher, Patricia, additional, Keerio, Allah Dino, additional, Shackcloth, Michael, additional, Gosney, John, additional, Postmus, Pieter, additional, Feeney, Sarah, additional, Asante-Siaw, Julius, additional, Aerts, Hugo J.W.L., additional, Dentro, Stefan, additional, and Dessimoz, Christophe, additional

Published
2017
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48. Defining the mechanisms of response and resistance to anti-PD-1 therapy: An exploratory phase II study of pembrolizumab in advanced melanoma (ADAPTeM).

Author

Joshi, Kroopa, primary, Furness, Andrew J.S., additional, Oakes, Theres, additional, Heather, James, additional, Spain, Lavinia Anne, additional, Wong, Yien Ning Sophia, additional, Ben Aissa, Assma, additional, Stares, Mark, additional, Smith, Myles JF, additional, Strauss, Dirk C, additional, Hayes, Andrew J, additional, Marafioti, Teresa, additional, Turajlic, Samra, additional, Gore, Martin Eric, additional, Peggs, Karl, additional, Chain, Benjamin, additional, Quezada, Sergio, additional, and Larkin, James M. G., additional

Published
2016
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49. Preoperative staging of the axilla.

Author

Wong, Yien Ning Sophia, Wilson, Robin, and Rusby, Jennifer E.

Subjects
*ULTRASONIC imaging, *BREAST cancer treatment, *METASTASIS, *NEEDLE biopsy, *AXILLA, *LYMPH nodes, *TUMORS
Abstract

The article discusses the significance of preoperative staging of the axilla in the management of breast cancer with axillary metastases. It highlights axillary lymph node staging as the single most significant prognostic indicator for breast cancer. It also notes that several clinical studies have shown that axillary ultrasound (AUS) with or without fine-needle aspiration cytology (FNAC) can be used to distinguish women with axillary nodal metastases.

Published
2010

50. Publisher Correction: Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer

Author

Joshi, Kroopa, de Massy, Marc Robert, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, Hatipoglu, Emine, Oakes, Theres, Rosenthal, Rachel, Peacock, Thomas, Ronel, Tahel, Noursadeghi, Mahdad, Turati, Virginia, Furness, Andrew J. S., Georgiou, Andrew, Wong, Yien Ning Sophia, Ben Aissa, Assma, Sunderland, Mariana Werner, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai J., Wilson, Gareth A., Hiley, Crispin T., Ghorani, Ehsan, Guerra-Assunção, José Afonso, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S., McGranahan, Nicholas, Swanton, Charles, Quezada, Sergio A., and Chain, Benny

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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