46 results on '"Reading, James L"'
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2. Tumor heterogeneity impairs immunogenicity in mismatch repair deficient tumors
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Reading, James L., Caswell, Deborah R., and Swanton, Charles
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- 2023
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3. Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
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Holm, Jeppe Sejerø, Funt, Samuel A., Borch, Annie, Munk, Kamilla Kjærgaard, Bjerregaard, Anne-Mette, Reading, James L., Maher, Colleen, Regazzi, Ashley, Wong, Phillip, Al-Ahmadie, Hikmat, Iyer, Gopa, Tamhane, Tripti, Bentzen, Amalie Kai, Herschend, Nana Overgaard, De Wolf, Susan, Snyder, Alexandra, Merghoub, Taha, Wolchok, Jedd D., Nielsen, Morten, Rosenberg, Jonathan E., Bajorin, Dean F., and Hadrup, Sine Reker
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- 2022
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4. Autoreactive T cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and re-emerging phenotype is associated with graft function
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Sabbah, Shereen, Liew, Aaron, Brooks, Augustin M., Kundu, Rhiannon, Reading, James L., Flatt, Anneliese, Counter, Claire, Choudhary, Pratik, Forbes, Shareen, Rosenthal, Miranda J., Rutter, Martin K., Cairns, Stephanie, Johnson, Paul, Casey, John, Peakman, Mark, Shaw, James A., and Tree, Timothy I.M.
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- 2021
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5. Early human lung immune cell development and its role in epithelial cell fate
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Barnes, Josephine L., primary, Yoshida, Masahiro, additional, He, Peng, additional, Worlock, Kaylee B., additional, Lindeboom, Rik G.H., additional, Suo, Chenqu, additional, Pett, J. Patrick, additional, Wilbrey-Clark, Anna, additional, Dann, Emma, additional, Mamanova, Lira, additional, Richardson, Laura, additional, Polanski, Krzysztof, additional, Pennycuick, Adam, additional, Allen-Hyttinen, Jessica, additional, Herczeg, Iván T., additional, Arzili, Romina, additional, Hynds, Robert E., additional, Teixeira, Vitor H., additional, Haniffa, Muzlifah, additional, Lim, Kyungtae, additional, Sun, Dawei, additional, Rawlins, Emma L., additional, Oliver, Amanda J., additional, Lyons, Paul A., additional, Marioni, John C., additional, Ruhrberg, Christiana, additional, Tuong, Zewen Kelvin, additional, Clatworthy, Menna R., additional, Reading, James L., additional, Janes, Sam M., additional, Teichmann, Sarah A., additional, Meyer, Kerstin B., additional, and Nikolić, Marko Z., additional
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- 2023
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6. 1032 Early remodelling of CD4 T cell differentiation in lung squamous carcinogenesis
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Sahwangarrom, Teerapon, primary, Marin, Claudia Peinador, additional, Gamble, Sam, additional, Whiteman, Zoe, additional, Ung, Seng, additional, Kalinke, Lukas, additional, Alhendi, Ahmed, additional, Pennycuick, Adam, additional, Lopez, Sandra Gomez, additional, Enica, Andrei, additional, Rogers, Amber, additional, Davies, Kate, additional, Foster, Kane, additional, Bentzen, Amalie Kai, additional, Przybilla, Moritz, additional, Gowers, Kate, additional, Teixeira, Vitor, additional, Campbell, Peter, additional, Vanhaesebroeck, Bart, additional, Janes, Sam, additional, and Reading, James L, additional
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- 2023
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7. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer
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Joshi, Kroopa, Robert de Massy, Marc, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, and Hatipoglu, Emine
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Gene mutations -- Research ,T cells -- Receptors ,Antigen receptors, T cell -- Research ,Immunotherapy -- Usage ,Lung cancer, Non-small cell -- Genetic aspects -- Care and treatment ,Biological sciences ,Health - 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.sup.+ 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. A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy., Author(s): Kroopa Joshi [sup.1] [sup.2] , Marc Robert de Massy [sup.1] , Mazlina Ismail [sup.3] , James L. Reading [sup.1] , Imran Uddin [sup.3] , Annemarie Woolston [sup.3] , Emine [...]
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- 2019
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8. The T cell differentiation landscape is shaped by tumour mutations in lung cancer
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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.
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- 2020
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9. Neoantigen-directed immune escape in lung cancer evolution
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Rosenthal, Rachel, Cadieux, Elizabeth Larose, Salgado, Roberto, Bakir, Maise Al, Moore, David A., Hiley, Crispin T., Lund, Tom, Tanić, Miljana, Reading, James L., Joshi, Kroopa, Henry, Jake Y., Ghorani, Ehsan, Wilson, Gareth A., Birkbak, Nicolai J., Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Szallasi, Zoltan, Loi, Sherene, Hellmann, Matthew D., Feber, Andrew, Chain, Benny, Herrero, Javier, Quezada, Sergio A., Demeulemeester, Jonas, Van Loo, Peter, Beck, Stephan, McGranahan, Nicholas, Swanton, Charles, and The TRACERx consortium
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- 2019
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10. Escape from nonsense-mediated decay associates with anti-tumor immunogenicity
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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
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- 2020
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11. Body composition and lung cancer-associated cachexia in TRACERx
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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
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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
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- 2023
12. The evolution of non-small cell lung cancer metastases in TRACERx
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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
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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
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- 2023
13. The evolution of lung cancer and impact of subclonal selection in TRACERx
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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
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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
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- 2023
14. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
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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
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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
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- 2023
15. Early human lung immune cell development and its role in epithelial cell fate
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Barnes, Josephine L., primary, He, Peng, additional, Yoshida, Masahiro, additional, Worlock, Kaylee B., additional, Lindeboom, Rik G.H., additional, Suo, Chenqu, additional, Pett, J. Patrick, additional, Wilbrey-Clark, Anna, additional, Dann, Emma, additional, Mamanova, Lira, additional, Richardson, Laura, additional, Oliver, Amanda J., additional, Pennycuick, Adam, additional, Allen-Hyttinen, Jessica, additional, Herczeg, Iván T., additional, Hynds, Robert E., additional, Teixeira, Vitor H., additional, Haniffa, Muzlifah, additional, Lim, Kyungtae, additional, Sun, Dawei, additional, Rawlins, Emma L., additional, Polanski, Krzysztof, additional, Lyons, Paul A., additional, Marioni, John C., additional, Tuong, Zewen Kelvin, additional, Clatworthy, Menna R., additional, Reading, James L., additional, Janes, Sam M., additional, Teichmann, Sarah A., additional, Meyer, Kerstin B., additional, and Nikolić, Marko Z., additional
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- 2022
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16. 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)
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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
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- 2022
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17. Abstract 6113: Spatially resolved biomarker detection on single cells in TRACERx using multiplex imaging
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Angelova, Mihaela, primary, Enfield, Katey, additional, Magness, Alastair, additional, Colliver, Emma, additional, Shimato, Masako, additional, Lee, Claudia, additional, Moore, David A., additional, Van Maldegem, Febe, additional, Hobson, Philip, additional, Levi, Dina, additional, Reading, James L., additional, Hiley, Crispin T., additional, Downward, Julian, additional, Sahai, Erik, additional, and Swanton, Charles, additional
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- 2022
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18. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma
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Au, Lewis, Hatipoglu, Emine, Robert De Massy, Marc, Litchfield, Kevin, Beattie, Gordon, Rowan, Andrew, Schnidrig, Desiree, Thompson, Rachael, Byrne, Fiona, Horswell, Stuart, Fotiadis, Nicos, Hazell, Steve, Nicol, David, Shepherd, Scott TC, Fendler, Annika, Mason, Robert, Del Rosario, Lyra, Edmonds, Kim, Lingard, Karla, Sarker, Sarah, Mangwende, Mary, Carlyle, Eleanor, Attig, Jan, Joshi, Kroopa, Uddin, Imran, Becker, Pablo D, Sunderland, Mariana Werner, Akarca, Ayse, Puccio, Ignazio, Yang, William W, Lund, Tom, Dhillon, Kim, Vasquez, Marcos Duran, Ghorani, Ehsan, Xu, Hang, Spencer, Charlotte, López, José I, Green, Anna, Mahadeva, Ula, Borg, Elaine, Mitchison, Miriam, Moore, David A, Proctor, Ian, Falzon, Mary, Pickering, Lisa, Furness, Andrew JS, Reading, James L, Salgado, Roberto, Marafioti, Teresa, Jamal-Hanjani, Mariam, PEACE Consortium, Kassiotis, George, Chain, Benny, Larkin, James, Swanton, Charles, Quezada, Sergio A, Turajlic, Samra, TRACERx Renal Consortium, and Apollo - University of Cambridge Repository
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multiregion ,Receptors, Antigen, T-Cell ,clear cell renal cell carcinoma ,CD8-Positive T-Lymphocytes ,autopsy ,Clinical Trials, Phase II as Topic ,Exome Sequencing ,Tumor Microenvironment ,Humans ,TCR clonal replacement ,Prospective Studies ,TCR clonal maintenance ,Carcinoma, Renal Cell ,Immune Checkpoint Inhibitors ,nivolumab ,Sequence Analysis, RNA ,Gene Expression Profiling ,Endogenous Retroviruses ,Genomics ,Kidney Neoplasms ,human endogenous retrovirus ,Drug Resistance, Neoplasm ,anti-PD-1 ,Tumor Escape ,T cell receptor ,Single-Cell Analysis - Abstract
ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.
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- 2021
19. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma
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Au, Lewis, primary, Hatipoglu, Emine, additional, Robert de Massy, Marc, additional, Litchfield, Kevin, additional, Beattie, Gordon, additional, Rowan, Andrew, additional, Schnidrig, Desiree, additional, Thompson, Rachael, additional, Byrne, Fiona, additional, Horswell, Stuart, additional, Fotiadis, Nicos, additional, Hazell, Steve, additional, Nicol, David, additional, Shepherd, Scott T.C., additional, Fendler, Annika, additional, Mason, Robert, additional, Del Rosario, Lyra, additional, Edmonds, Kim, additional, Lingard, Karla, additional, Sarker, Sarah, additional, Mangwende, Mary, additional, Carlyle, Eleanor, additional, Attig, Jan, additional, Joshi, Kroopa, additional, Uddin, Imran, additional, Becker, Pablo D., additional, Sunderland, Mariana Werner, additional, Akarca, Ayse, additional, Puccio, Ignazio, additional, Yang, William W., additional, Lund, Tom, additional, Dhillon, Kim, additional, Vasquez, Marcos Duran, additional, Ghorani, Ehsan, additional, Xu, Hang, additional, Spencer, Charlotte, additional, López, José I., additional, Green, Anna, additional, Mahadeva, Ula, additional, Borg, Elaine, additional, Mitchison, Miriam, additional, Moore, David A., additional, Proctor, Ian, additional, Falzon, Mary, additional, Pickering, Lisa, additional, Furness, Andrew J.S., additional, Reading, James L., additional, Salgado, Roberto, additional, Marafioti, Teresa, additional, Jamal-Hanjani, Mariam, additional, Kassiotis, George, additional, Chain, Benny, additional, Larkin, James, additional, Swanton, Charles, additional, Quezada, Sergio A., additional, Turajlic, Samra, additional, Abbosh, Chris, additional, Shiu, Kai-Keen, additional, Bridgewater, John, additional, Hochhauser, Daniel, additional, Forster, Martin, additional, Lee, Siow-Ming, additional, Ahmad, Tanya, additional, Papadatos-Pastos, Dionysis, additional, Janes, Sam, additional, Van Loo, Peter, additional, Enfield, Katey, additional, McGranahan, Nicholas, additional, Huebner, Ariana, additional, Beck, Stephan, additional, Parker, Peter, additional, Walczak, Henning, additional, Enver, Tariq, additional, Hynds, Rob, additional, Sinclair, Ron, additional, Lok, Chi-wah, additional, Rhodes, Zoe, additional, Moore, David, additional, Khiroya, Reena, additional, Trevisan, Giorgia, additional, Ellery, Peter, additional, Linch, Mark, additional, Brandner, Sebastian, additional, Hiley, Crispin, additional, Veeriah, Selvaraju, additional, Razaq, Maryam, additional, Shaw, Heather, additional, Attard, Gert, additional, Akther, Mita Afroza, additional, Naceur-Lombardelli, Cristina, additional, Manzano, Lizi, additional, Al-Bakir, Maise, additional, Summan, Simranpreet, additional, Kanu, Nnenna, additional, Ward, Sophie, additional, Asghar, Uzma, additional, Lim, Emilia, additional, Gishen, Faye, additional, Tookman, Adrian, additional, Stone, Paddy, additional, Stirling, Caroline, additional, Hunter, Nikki, additional, Vaughan, Sarah, additional, Spain, Lavinia, additional, Yan, Haixi, additional, Shum, Ben, additional, Yousaf, Nadia, additional, Popat, Sanjay, additional, Curtis, Olivia, additional, Stamp, Gordon, additional, Toncheva, Antonia, additional, Nye, Emma, additional, Murra, Aida, additional, Korteweg, Justine, additional, Josephs, Debra, additional, Chandra, Ashish, additional, Spicer, James, additional, Stewart, Ruby, additional, Iredale, Lara-Rose, additional, Mackay, Tina, additional, Deakin, Ben, additional, Enting, Debra, additional, Rudman, Sarah, additional, Ghosh, Sharmistha, additional, Karapagniotou, Lena, additional, Pintus, Elias, additional, Tutt, Andrew, additional, Howlett, Sarah, additional, Michalarea, Vasiliki, additional, Brenton, James, additional, Caldas, Carlos, additional, Fitzgerald, Rebecca, additional, Jimenez-Linan, Merche, additional, Provenzano, Elena, additional, Cluroe, Alison, additional, Stewart, Grant, additional, Watts, Colin, additional, Gilbertson, Richard, additional, McDermott, Ultan, additional, Tavare, Simon, additional, Beddowes, Emma, additional, Roxburgh, Patricia, additional, Biankin, Andrew, additional, Chalmers, Anthony, additional, Fraser, Sioban, additional, Oien, Karin, additional, Kidd, Andrew, additional, Blyth, Kevin, additional, Krebs, Matt, additional, Blackhall, Fiona, additional, Summers, Yvonne, additional, Dive, Caroline, additional, Marais, Richard, additional, Gomes, Fabio, additional, Carter, Mat, additional, Dransfield, Jo, additional, Le Quesne, John, additional, Fennell, Dean, additional, Shaw, Jacqui, additional, Naidu, Babu, additional, Baijal, Shobhit, additional, Tanchel, Bruce, additional, Langman, Gerald, additional, Robinson, Andrew, additional, Collard, Martin, additional, Cockcroft, Peter, additional, Ferris, Charlotte, additional, Bancroft, Hollie, additional, Kerr, Amy, additional, Middleton, Gary, additional, Webb, Joanne, additional, Kadiri, Salma, additional, Colloby, Peter, additional, Olisemeke, Bernard, additional, Wilson, Rodelaine, additional, Tomlinson, Ian, additional, Jogai, Sanjay, additional, Ottensmeier, Christian, additional, Harrison, David, additional, Loda, Massimo, additional, Flanagan, Adrienne, additional, McKenzie, Mairead, additional, Hackshaw, Allan, additional, Ledermann, Jonathan, additional, Chan, Kitty, additional, Sharp, Abby, additional, Farrelly, Laura, additional, Bridger, Hayley, additional, Challacombe, Ben, additional, Chowdhury, Simon, additional, Drake, William, additional, Fernando, Archana, additional, Harrison-Phipps, Karen, additional, Hill, Peter, additional, Horsfield, Catherine, additional, O'Brien, Tim, additional, Olsburgh, Jonathon, additional, Polson, Alexander, additional, Varia, Mary, additional, and Verma, Hema, additional
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- 2021
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20. Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell Frequency and Function in Individuals With Long-standing Type 1 Diabetes
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Yang, Jennie H.M., Cutler, Antony J., Ferreira, Ricardo C., Reading, James L., Cooper, Nicholas J., Wallace, Chris, Clarke, Pamela, Smyth, Deborah J., Boyce, Christopher S., Gao, Guo-Jian, Todd, John A., Wicker, Linda S., and Tree, Timothy I.M.
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- 2015
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21. Augmented Expansion of Treg Cells From Healthy and Autoimmune Subjects via Adult Progenitor Cell Co-Culture
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Reading, James L., primary, Roobrouck, Valerie D., additional, Hull, Caroline M., additional, Becker, Pablo Daniel, additional, Beyens, Jelle, additional, Valentin-Torres, Alice, additional, Boardman, Dominic, additional, Lamperti, Estefania Nova, additional, Stubblefield, Samantha, additional, Lombardi, Giovanna, additional, Deans, Robert, additional, Ting, Anthony E., additional, and Tree, Timothy, additional
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- 2021
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22. Abstract 67: Paralleled convergence of antigen load, disease progression and systemic T cell exhaustion in lung cancer and HIV-1 infection
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Reading, James L., primary, Rosenthal, Rachel, additional, Black, Lucas, additional, Ung, Seng Kuong, additional, Streatfield, Claire, additional, Wooding, Dominic, additional, Esbjornsson, Joakim, additional, Hunter, Eric, additional, Quezada, Sergio A., additional, Hare, Jonathan, additional, and Swanton, Charles, additional
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- 2021
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23. Tracking Cancer Evolution through the Disease Course
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Bailey, Chris, primary, Black, James R.M., additional, Reading, James L., additional, Litchfield, Kevin, additional, Turajlic, Samra, additional, McGranahan, Nicholas, additional, Jamal-Hanjani, Mariam, additional, and Swanton, Charles, additional
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- 2021
- Full Text
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24. Determinants of anti-PD1 response and resistance in clear cell renal cell carcinoma
- Author
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Au, Lewis, primary, Hatipoglu, Emine, additional, de Massy, Marc Robert, additional, Litchfield, Kevin, additional, Rowan, Andrew, additional, Thompson, Rachael, additional, Schnidrig, Desiree, additional, Byrne, Fiona, additional, Beattie, Gordon, additional, Horswell, Stuart, additional, Fotiadis, Nicos, additional, Hazell, Steve, additional, Nicol, David, additional, Shepherd, Scott Thomas Colville, additional, Fendler, Annika, additional, Mason, Robert, additional, Attig, Jan, additional, Joshi, Kroopa, additional, Uddin, Imran, additional, Becker, Pablo, additional, Sunderland, Mariana Werner, additional, Akarca, Ayse, additional, Puccio, Ignazio, additional, Yang, William, additional, Lund, Tom, additional, Dhillon, Kim, additional, Vasquez, Marcos Duran, additional, Ghorani, Ehsan, additional, Xu, Hang, additional, López, José Ignacio, additional, Green, Anna, additional, Mahadeva, Ula, additional, Borg, Elaine, additional, Mitchison, Miriam, additional, Moore, David, additional, Proctor, Ian, additional, Falzon, Mary, additional, Furness, Andrew, additional, Pickering, Lisa, additional, Reading, James L., additional, Salgado, Roberto, additional, Marafioti, Teresa, additional, Jamal-Hanjani, Mariam, additional, Kassiotis, George, additional, Chain, Benny, additional, Larkin, James, additional, Swanton, Charles, additional, Quezada, Sergio A, additional, and Turajlic, Samra, additional
- Published
- 2021
- Full Text
- View/download PDF
25. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition
- Author
-
Litchfield, Kevin, primary, Reading, James L., additional, Puttick, Clare, additional, Thakkar, Krupa, additional, Abbosh, Chris, additional, Bentham, Robert, additional, Watkins, Thomas B.K., additional, Rosenthal, Rachel, additional, Biswas, Dhruva, additional, Rowan, Andrew, additional, Lim, Emilia, additional, Al Bakir, Maise, additional, Turati, Virginia, additional, Guerra-Assunção, José Afonso, additional, Conde, Lucia, additional, Furness, Andrew J.S., additional, Saini, Sunil Kumar, additional, Hadrup, Sine R., additional, Herrero, Javier, additional, Lee, Se-Hoon, additional, Van Loo, Peter, additional, Enver, Tariq, additional, Larkin, James, additional, Hellmann, Matthew D., additional, Turajlic, Samra, additional, Quezada, Sergio A., additional, McGranahan, Nicholas, additional, and Swanton, Charles, additional
- Published
- 2021
- Full Text
- View/download PDF
26. Publisher Correction: Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer
- Author
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Joshi, Kroopa, de Massy, Marc Robert, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, and Hatipoglu, Emine
- Subjects
Biological sciences ,Health - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper., Author(s): Kroopa Joshi [sup.1] [sup.2] , Marc Robert de Massy [sup.1] , Mazlina Ismail [sup.3] , James L. Reading [sup.1] , Imran Uddin [sup.3] , Annemarie Woolston [sup.3] , Emine [...]
- Published
- 2020
- Full Text
- View/download PDF
27. Meta-analysis of tumor and T cell intrinsic mechanisms of sensitization to checkpoint inhibition
- Author
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Litchfield, Kevin, primary, Reading, James L., additional, Puttick, Clare, additional, Abbosh, Chris, additional, Bentham, Robert, additional, Watkins, Thomas B. K., additional, Rosenthal, Rachel, additional, Biswas, Dhruva, additional, Lim, Emilia, additional, AL-Bakir, Maise, additional, Turati, Virginia, additional, Guerra-Assunção, José Afonso, additional, Conde, Lucia, additional, Furness, Andrew J.S., additional, Saini, Sunil Kumar, additional, Hadrup, Sine R, additional, Herrero, Javier, additional, Rowan, Andrew, additional, Enver, Tariq, additional, Hellmann, Matthew D., additional, Larkin, James, additional, Turajlic, Samra, additional, Quezada, Sergio, additional, McGranahan, Nicholas, additional, and Swanton, Charles, additional
- Published
- 2020
- Full Text
- View/download PDF
28. Interrogation of neoantigen-specific CD8 T cells in peripheral blood following PD-L1 blockade in patients with metastatic urothelial carcinoma (mUC).
- Author
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Holm, Jeppe Sejerø, primary, Funt, Samuel Aaron, additional, Bjerregaard, Anne-Mette, additional, Reading, James L., additional, Maher, Colleen Anne, additional, Regazzi, Ashley Marie, additional, Wong, Phillip, additional, Al-Ahmadie, Hikmat, additional, Overgaard, Nana Haahr, additional, Tamhane, Tripti, additional, Bentzen, Amalie Kai, additional, Snyder, Alexandra, additional, Merghoub, Taha, additional, Wolchok, Jedd D., additional, Nielsen, Morten, additional, Rosenberg, Jonathan E., additional, Bajorin, Dean F., additional, and Hadrup, Sine Reker, additional
- Published
- 2020
- Full Text
- View/download PDF
29. Neoantigen directed immune escape in lung cancer evolution
- Author
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Rosenthal Rachel, Cadieux Elizabeth L, Roberto Salgado, Al Bakir Maise, Moore David A., Hiley Crispin T., Lund Tom, Tanić Miljana, Reading James L, Joshi Kroopa, Henry Jake Y, and TRACERx Consortium
- Subjects
immunology ,genetics ,pathology ,human ,prognosis ,Adenocarcinoma ,lung neoplasms - Abstract
The interplay between an evolving cancer and the dynamic immune-microenvironment remains unclear. Here, we analyze 258 regions from 88 early-stage untreated non-small cell lung cancers (NSCLCs) using RNAseq and pathology tumor infiltrating lymphocyte estimates. The immunemicroenvironment was variable both between and within patients’ tumors. Diverse immune selection pressures were associated with different mechanisms of neoantigen presentation dysfunction restricted to distinct microenvironments. Sparsely infiltrated tumors exhibited evidence for historical immunoediting, with a waning of neoantigen-editing during tumor evolution, or copy number loss of historically clonal neoantigens. Immune-infiltrated tumor regions exhibited ongoing immunoediting, with either HLA LOH or depletion of expressed neoantigens. Promoter hypermethylation of genes harboring neoantigens was identified as an epigenetic mechanism of immunoediting. Our results suggest the immune-microenvironment exerts a strong selection pressure in early stage, untreated NSCLCs, producing multiple routes to immune evasion, which are clinically relevant, forecasting poor disease-free survival in multivariate analysis.
- Published
- 2019
30. Association of the imbalance between early and late differentiated intra-tumor CD4 T cells with mutational burden in non-small cell lung cancer.
- Author
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Ghorani, Ehsan, primary, Reading, James L., additional, Henry, Jake Y., additional, Robert De Massy, Marc, additional, Rosenthal, Rachel, additional, Furness, Andrew J.S., additional, Ben Aissa, Assma, additional, Jamal-Hanjani, Mariam, additional, Birkbak, Nicolai, additional, Wilson, Gareth, additional, Salgado, Roberto, additional, Lund, Tom, additional, Hiley, Crispin T., additional, Loi, Sherene, additional, Hackshaw, Allan, additional, McGranahan, Nicholas, additional, Chain, Benjamin M., additional, Peggs, Karl S., additional, Swanton, Charles, additional, and Quezada, Sergio A., additional
- Published
- 2019
- Full Text
- View/download PDF
31. WFDC1 expression identifies memory CD4 T- lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions
- Author
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Reddy Shalini, Reading James L, Thorborn Georgina, Alvarez Raymond A, and Vyakarnam Annapurna
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Elucidating mechanisms that promote HIV-1 transfer between CD4+ T-lymphocytes and their subsequent loss is of importance to HIV-1 pathogenesis. We recently reported that whey acidic protein, ps20, promotes cell-free HIV-1 spread through ICAM-1 modulation. Since ICAM-1 is pivotal in cell conjugation and intercellular HIV-1 transfer, this study examines ps20 effects on HIV-1 spread between T lymphocytes. Results We demonstrate intrinsic ps20 variability in primary CD4+ T-lymphocyte clonal populations and a significant positive correlation between endogenous ps20 levels and virus transfer involving fusion resulting in a spreading infection that could be reversed by the addition of reverse transcriptase inhibitors. Blocking anti-ps20 antibody or siRNA mediated ps20 knockdown, significantly reduced virus transfer. Conversely, virus transfer was promoted by ectopic ps20 expression or by exogenous addition of recombinant ps20. A higher frequency of virological synapse formation was evident in cocultures of HIV-1 infected donor T-cells with ps20high v ps20low/intermediate targets. Blocking ps20 inhibited T-lymphocyte conjugate formation and ICAM-1 expression, and was as potent as ICAM-1 in inhibiting HIV-1 transfer. Conclusions Therefore ps20 is a novel marker of CD4+ T-cells rendered vulnerable to HIV-1 infection by regulating the fundamental biologic process of intercellular conjugate formation and consequently of potential importance in HIV-1 pathogenesis.
- Published
- 2011
- Full Text
- View/download PDF
32. Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment
- Author
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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
- Full Text
- View/download PDF
33. 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
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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
- Full Text
- View/download PDF
34. Multipotent Adult Progenitor Cells Suppress T Cell Activation in In Vivo Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner
- Author
-
Carty, Fiona, primary, Corbett, Jennifer M., additional, Cunha, João Paulo M. C. M., additional, Reading, James L., additional, Tree, Timothy I. M., additional, Ting, Anthony E., additional, Stubblefield, Samantha R., additional, and English, Karen, additional
- Published
- 2018
- Full Text
- View/download PDF
35. The function and dysfunction of memory CD8+T cells in tumor immunity
- Author
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Reading, James L., primary, Gálvez-Cancino, Felipe, additional, Swanton, Charles, additional, Lladser, Alvaro, additional, Peggs, Karl S., additional, and Quezada, Sergio A., additional
- Published
- 2018
- Full Text
- View/download PDF
36. Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell Frequency and Function in Individuals With Long-standing Type 1 Diabetes
- Author
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Yang, Jennie HM, Cutler, Antony J, Ferreira, Ricardo C, Reading, James L, Cooper, Nicholas J, Wallace, Chris, Clarke, Pamela, Smyth, Deborah J, Boyce, Christopher S, Gao, Guo-Jian, Todd, John A, Wicker, Linda S, Tree, Timothy IM, Wallace, Chris [0000-0001-9755-1703], and Apollo - University of Cambridge Repository
- Subjects
Protein Tyrosine Phosphatase, Non-Receptor Type 2 ,Diabetes Mellitus, Type 1 ,Genotype ,Interleukin-2 Receptor alpha Subunit ,Humans ,Interleukin-2 ,Polymorphism, Single Nucleotide ,T-Lymphocytes, Regulatory ,Signal Transduction - Abstract
Defective immune homeostasis in the balance between FOXP3+ regulatory T cells (Tregs) and effector T cells is a likely contributing factor in the loss of self-tolerance observed in type 1 diabetes (T1D). Given the importance of interleukin-2 (IL-2) signaling in the generation and function of Tregs, observations that polymorphisms in genes in the IL-2 pathway associate with T1D and that some individuals with T1D exhibit reduced IL-2 signaling indicate that impairment of this pathway may play a role in Treg dysfunction and the pathogenesis of T1D. Here, we have examined IL-2 sensitivity in CD4+ T-cell subsets in 70 individuals with long-standing T1D, allowing us to investigate the effect of low IL-2 sensitivity on Treg frequency and function. IL-2 responsiveness, measured by STAT5a phosphorylation, was a very stable phenotype within individuals but exhibited considerable interindividual variation and was influenced by T1D-associated PTPN2 gene polymorphisms. Tregs from individuals with lower IL-2 signaling were reduced in frequency, were less able to maintain expression of FOXP3 under limiting concentrations of IL-2, and displayed reduced suppressor function. These results suggest that reduced IL-2 signaling may be used to identify patients with the highest Treg dysfunction and who may benefit most from IL-2 immunotherapy.
- Published
- 2015
37. Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis
- Author
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Turajlic, Samra, primary, Litchfield, Kevin, additional, Xu, Hang, additional, Rosenthal, Rachel, additional, McGranahan, Nicholas, additional, Reading, James L, additional, Wong, Yien Ning S, additional, Rowan, Andrew, additional, Kanu, Nnennaya, additional, Al Bakir, Maise, additional, Chambers, Tim, additional, Salgado, Roberto, additional, Savas, Peter, additional, Loi, Sherene, additional, Birkbak, Nicolai J, additional, Sansregret, Laurent, additional, Gore, Martin, additional, Larkin, James, additional, Quezada, Sergio A, additional, and Swanton, Charles, additional
- Published
- 2017
- Full Text
- View/download PDF
38. Too Much of a Good Thing? Chronic IFN Fuels Resistance to Cancer Immunotherapy
- Author
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Reading, James L., primary and Quezada, Sergio A., additional
- Published
- 2016
- Full Text
- View/download PDF
39. Suppression of IL-7-dependent Effector T-cell Expansion by Multipotent Adult Progenitor Cells and PGE2
- Author
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Reading, James L, primary, Vaes, Bart, additional, Hull, Caroline, additional, Sabbah, Shereen, additional, Hayday, Thomas, additional, Wang, Nancy S, additional, DiPiero, Anthony, additional, Lehman, Nicholas A, additional, Taggart, Jen M, additional, Carty, Fiona, additional, English, Karen, additional, Pinxteren, Jef, additional, Deans, Robert, additional, Ting, Anthony E, additional, and Tree, Timothy I M, additional
- Published
- 2015
- Full Text
- View/download PDF
40. The function and dysfunction of memory CD8+ T cells in tumor immunity.
- Author
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Reading, James L., Gálvez‐Cancino, Felipe, Swanton, Charles, Lladser, Alvaro, Peggs, Karl S., and Quezada, Sergio A.
- Subjects
- *
TUMOR immunology , *T cells , *IMMUNOLOGIC memory , *CD8 antigen , *CANCER immunotherapy , *EPIGENETICS - Abstract
ABSTRACT: The generation and maintenance of CD8+ T cell memory is crucial to long‐term host survival, yet the basic tenets of CD8+ T cell immunity are still being established. Recent work has led to the discovery of tissue‐resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8+ T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de‐repress the anti‐tumor response. However, the progress of immunotherapy is at a critical juncture, since the efficacy of immuno‐oncology agents remains confined to a fraction of patients and often fails to provide durable benefit. Unlocking the potential of immunotherapy requires the design of strategies that both induce a potent effector response and reliably forge stable, functional memory T cell pools capable of protecting from recurrence or relapse. It is therefore essential that basic and emerging concepts of memory T cell biology are rapidly and faithfully transposed to advance therapeutic development in cancer immunotherapy. This review highlights seminal and recent reports in CD8+ T cell memory and tumor immunology, and evaluates recent data from solid cancer specimens in the context of the key paradigms from preclinical models. We elucidate the potential significance of circulating effector cells poised downstream of neoantigen recognition and upstream of T cell dysfunction and propose that cells in this immunological ‘sweet spot’ may be key anti‐tumor effectors. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
41. Clinical-Grade Multipotent Adult Progenitor Cells Durably Control Pathogenic T Cell Responses in Human Models of Transplantation and Autoimmunity
- Author
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Reading, James L., primary, Yang, Jennie H. M., additional, Sabbah, Shereen, additional, Skowera, Ania, additional, Knight, Robin R., additional, Pinxteren, Jef, additional, Vaes, Bart, additional, Allsopp, Timothy, additional, Ting, Anthony E., additional, Busch, Sarah, additional, Raber, Amy, additional, Deans, Robert, additional, and Tree, Timothy I. M., additional
- Published
- 2013
- Full Text
- View/download PDF
42. Mesenchymal stromal cells as a means of controlling pathological T-cell responses in allogeneic islet transplantation
- Author
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Reading, James L., primary, Sabbah, Shereen, additional, Busch, Sarah, additional, and Tree, Timothy I.M., additional
- Published
- 2013
- Full Text
- View/download PDF
43. Whey acidic proteins (WAPs)
- Author
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Reading, James L., primary, Meyers, Adrienne F.A., additional, and Vyakarnam, Annapurna, additional
- Published
- 2012
- Full Text
- View/download PDF
44. WFDC1 expression identifies memory CD4 T- lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions
- Author
-
Alvarez, Raymond A, primary, Thorborn, Georgina, additional, Reading, James L, additional, Reddy, Shalini Kamu, additional, and Vyakarnam, Annapurna, additional
- Published
- 2011
- Full Text
- View/download PDF
45. WFDC1 expression identifies memory CD4 Tlymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions.
- Author
-
Alvarez, Raymond A., Thorborn, Georgina, Reading, James L., Reddy, Shalini Kamu, and Vyakarnam, Annapurna
- Subjects
HIV infections ,LEUCOCYTES ,T cells ,PATHOGENIC microorganisms ,GENE expression - Abstract
Background: Elucidating mechanisms that promote HIV-1 transfer between CD4
+ T-lymphocytes and their subsequent loss is of importance to HIV-1 pathogenesis. We recently reported that whey acidic protein, ps20, promotes cell-free HIV-1 spread through ICAM-1 modulation. Since ICAM-1 is pivotal in cell conjugation and intercellular HIV-1 transfer, this study examines ps20 effects on HIV-1 spread between T lymphocytes. Results: We demonstrate intrinsic ps20 variability in primary CD4+ T-lymphocyte clonal populations and a significant positive correlation between endogenous ps20 levels and virus transfer involving fusion resulting in a spreading infection that could be reversed by the addition of reverse transcriptase inhibitors. Blocking anti-ps20 antibody or siRNA mediated ps20 knockdown, significantly reduced virus transfer. Conversely, virus transfer was promoted by ectopic ps20 expression or by exogenous addition of recombinant ps20. A higher frequency of virological synapse formation was evident in cocultures of HIV-1 infected donor T-cells with ps20high v ps20low/intermediate targets. Blocking ps20 inhibited T-lymphocyte conjugate formation and ICAM-1 expression, and was as potent as ICAM-1 in inhibiting HIV-1 transfer. Conclusions: Therefore ps20 is a novel marker of CD4+ T-cells rendered vulnerable to HIV-1 infection by regulating the fundamental biologic process of intercellular conjugate formation and consequently of potential importance in HIV-1 pathogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
- View/download PDF
46. Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.
- Author
-
Enfield KSS, Colliver E, Lee C, Magness A, Moore DA, Sivakumar M, Grigoriadis K, Pich O, Karasaki T, Hobson PS, Levi D, Veeriah S, Puttick C, Nye EL, Green M, Dijkstra KK, Shimato M, Akarca AU, Marafioti T, Salgado R, Hackshaw A, Jamal-Hanjani M, van Maldegem F, McGranahan N, Glass B, Pulaski H, Walk E, Reading JL, Quezada SA, Hiley CT, Downward J, Sahai E, Swanton C, and Angelova M
- Subjects
- Humans, T-Lymphocytes immunology, Myeloid Cells immunology, Female, Male, Immune Evasion, Lung Neoplasms immunology, Lung Neoplasms pathology, Lung Neoplasms genetics, Tumor Microenvironment immunology
- Abstract
Understanding the role of the tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs in treatment-naïve early-stage lung cancer using imaging mass cytometry in the TRACERx study (n = 81 patients/198 samples/2.3 million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterized by sparse lymphocytes and high tumor-associated neutrophil (TAN) infiltration, had tumor cells spatially separated from vasculature and exhibited low spatial intratumor heterogeneity. TAN-high LUSC had frequent PIK3CA mutations. TAN-high tumors harbored recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune, and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis., Significance: This study provides novel insights into the spatial organization of the lung cancer TME in the context of tumor immunogenicity, tumor heterogeneity, and cancer evolution. Pairing the tumor evolutionary history with the spatially resolved TME suggests mechanistic hypotheses for tumor progression and metastasis with implications for patient outcome and treatment. This article is featured in Selected Articles from This Issue, p. 897., (©2024 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2024
- Full Text
- View/download PDF
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