Search

Your search keyword '"Hiley, Crispin T"' showing total 134 results
Start Over Author "Hiley, Crispin T"
134 results on '"Hiley, Crispin T"'

2. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author

Hobor, Sebastijan, Al Bakir, Maise, Hiley, Crispin T., Skrzypski, Marcin, Frankell, Alexander M., Bakker, Bjorn, Watkins, Thomas B. K., Markovets, Aleksandra, Dry, Jonathan R., Brown, Andrew P., van der Aart, Jasper, van den Bos, Hilda, Spierings, Diana, Oukrif, Dahmane, Novelli, Marco, Chakrabarti, Turja, Rabinowitz, Adam H., Ait Hassou, Laila, Litière, Saskia, Kerr, D. Lucas, Tan, Lisa, Kelly, Gavin, Moore, David A., Renshaw, Matthew J., Venkatesan, Subramanian, Hill, William, Huebner, Ariana, Martínez-Ruiz, Carlos, Black, James R. M., Wu, Wei, Angelova, Mihaela, McGranahan, Nicholas, Downward, Julian, Chmielecki, Juliann, Barrett, Carl, Litchfield, Kevin, Chew, Su Kit, Blakely, Collin M., de Bruin, Elza C., Foijer, Floris, Vousden, Karen H., Bivona, Trever G., Hynds, Robert E., Kanu, Nnennaya, Zaccaria, Simone, Grönroos, Eva, and Swanton, Charles

Published
2024
Full Text
View/download PDF

3. Author Correction: 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 R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-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, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2024
Full Text
View/download PDF

4. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author

Ng, Kevin W., Boumelha, Jesse, Enfield, Katey S. S., Almagro, Jorge, Cha, Hongui, Pich, Oriol, Karasaki, Takahiro, Moore, David A., Salgado, Roberto, Sivakumar, Monica, Young, George, Molina-Arcas, Miriam, de Carné Trécesson, Sophie, Anastasiou, Panayiotis, Fendler, Annika, Au, Lewis, Shepherd, Scott T. C., Martínez-Ruiz, Carlos, Puttick, Clare, Black, James R. M., Watkins, Thomas B. K., Kim, Hyemin, Shim, Seohee, Faulkner, Nikhil, Attig, Jan, Veeriah, Selvaraju, Magno, Neil, Ward, Sophia, Frankell, Alexander M., Al Bakir, Maise, Lim, Emilia L., Hill, Mark S., Wilson, Gareth A., Cook, Daniel E., Birkbak, Nicolai J., Behrens, Axel, Yousaf, Nadia, Popat, Sanjay, Hackshaw, Allan, Hiley, Crispin T., Litchfield, Kevin, McGranahan, Nicholas, Jamal-Hanjani, Mariam, Larkin, James, Lee, Se-Hoon, Turajlic, Samra, Swanton, Charles, Downward, Julian, and Kassiotis, George

Published
2023
Full Text
View/download PDF

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

Author

Al Bakir, Maise, Huebner, Ariana, Martínez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas B. K., 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 M., 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 A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J., Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
Full Text
View/download PDF

6. 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 R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-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, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
Full Text
View/download PDF

7. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Author

Abbosh, Christopher, Frankell, Alexander M., Harrison, Thomas, Kisistok, Judit, Garnett, Aaron, Johnson, Laura, Veeriah, Selvaraju, Moreau, Mike, Chesh, Adrian, Chaunzwa, Tafadzwa L., Weiss, Jakob, Schroeder, Morgan R., Ward, Sophia, Grigoriadis, Kristiana, Shahpurwalla, Aamir, Litchfield, Kevin, Puttick, Clare, Biswas, Dhruva, Karasaki, Takahiro, Black, James R. M., Martínez-Ruiz, Carlos, Bakir, Maise Al, Pich, Oriol, Watkins, Thomas B. K., Lim, Emilia L., Huebner, Ariana, Moore, David A., Godin-Heymann, Nadia, L’Hernault, Anne, Bye, Hannah, Odell, Aaron, Roberts, Paula, Gomes, Fabio, Patel, Akshay J., Manzano, Elizabeth, Hiley, Crispin T., Carey, Nicolas, Riley, Joan, Cook, Daniel E., Hodgson, Darren, Stetson, Daniel, Barrett, J. Carl, Kortlever, Roderik M., Evan, Gerard I., Hackshaw, Allan, Daber, Robert D., Shaw, Jacqui A., Aerts, Hugo J. W. L., Licon, Abel, Stahl, Josh, Jamal-Hanjani, Mariam, Birkbak, Nicolai J., McGranahan, Nicholas, and Swanton, Charles

Published
2023
Full Text
View/download PDF

8. 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, Bakir, Maise Al, Watkins, Thomas B. K., 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., Martínez-Ruiz, Carlos, Black, James R. M., Biswas, Dhruva, Campbell, Brittany B., Lee, Claudia, Colliver, Emma, Enfield, Katey S. S., Hessey, Sonya, Hiley, Crispin T., Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J., Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad S., 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, and Jamal-Hanjani, Mariam

Published
2023
Full Text
View/download PDF

9. Olaparib, AZD1390, ceralasertib, saruparib and consolidation durvalumab (CONCORDE) phase Ib platform study of novel DNA damage response inhibitor (DDRi) agents in combination with radiotherapy in non-small cell lung cancer (NSCLC).

Author

Greystoke, Alastair, primary, Oughton, Jamie B., additional, Brown, Sarah R, additional, Butterworth, Karl, additional, Coyle, Victoria, additional, Franks, Kevin, additional, Hassani, Adam, additional, Harrow, Stephen, additional, Hatton, Matthew, additional, Hiley, Crispin T., additional, Kendall, Jessica, additional, Phillip, Rachel, additional, Norris, Matthew, additional, Ojo, Oluwaseun, additional, Shaw, Paul, additional, Walker, Fiona, additional, Yang, Huiqi, additional, Chalmers, Anthony J., additional, and Faivre-Finn, Corinne, additional

Published
2024
Full Text
View/download PDF

11. Using DNA sequencing data to quantify T cell fraction and therapy response

Author

Bentham, Robert, Litchfield, Kevin, Watkins, Thomas B. K., Lim, Emilia L., Rosenthal, Rachel, Martínez-Ruiz, Carlos, Hiley, Crispin T., Bakir, Maise Al, Salgado, Roberto, Moore, David A., Jamal-Hanjani, Mariam, Birkbak, Nicolai J., Escudero, Mickael, Stewart, Aengus, Rowan, Andrew, and Goldman, Jacki

Subjects
Nucleotide sequencing -- Methods, T cells -- Physiological aspects -- Genetic aspects, Cellular therapy -- Methods, DNA sequencing -- Methods, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy.sup.1,2. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC tool (T cell ExTRECT), a method for estimation of T cell fraction from WES samples using a signal from T cell receptor excision circle (TREC) loss during V(D)J recombination of the T cell receptor-[alpha] gene (TCRA (also known as TRA)). TCRA T cell fraction correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females than in males and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma. Using a meta-analysis of tumours treated with immunotherapy, we show that tumour TCRA T cell fraction predicts immunotherapy response, providing value beyond measuring tumour mutational burden. Applying T cell ExTRECT to a multi-sample pan-cancer cohort reveals a high diversity of the degree of immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, is associated with reduced TCRA T cell fraction. T cell ExTRECT provides a cost-effective technique to characterize immune infiltrate alongside somatic changes. A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy., Author(s): Robert Bentham [sup.1] [sup.2] , Kevin Litchfield [sup.2] [sup.3] , Thomas B. K. Watkins [sup.4] , Emilia L. Lim [sup.2] [sup.4] , Rachel Rosenthal [sup.4] , Carlos Martínez-Ruiz [sup.1] [...]

Published
2021
Full Text
View/download PDF

12. CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer

Author

Walls, Gerard M., Oughton, Jamie B., Chalmers, Anthony J., Brown, Sarah, Collinson, Fiona, Forster, Martin D., Franks, Kevin N., Gilbert, Alexandra, Hanna, Gerard G., Hannaway, Nicola, Harrow, Stephen, Haswell, Tom, Hiley, Crispin T., Hinsley, Samantha, Krebs, Matthew, Murden, Geraldine, Phillip, Rachel, Ryan, Anderson J., Salem, Ahmed, Sebag-Montefoire, David, Shaw, Paul, Twelves, Chris J., Walker, Katrina, Young, Robin J., Faivre-Finn, Corinne, and Greystoke, Alastair

Published
2020
Full Text
View/download PDF

13. A clonal expression biomarker associates with lung cancer mortality

Author

Biswas, Dhruva, Birkbak, Nicolai J., Rosenthal, Rachel, Hiley, Crispin T., Lim, Emilia L., Papp, Krisztian, and Boeing, Stefan

Subjects
RNA sequencing -- Usage, Lung cancer -- Genetic aspects -- Care and treatment, Genetic transcription -- Research, Biological markers -- Research, Biological sciences, Health
Abstract

An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage.sup.1. Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types.sup.2-6. Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types. TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers., Author(s): Dhruva Biswas [sup.1] [sup.2] [sup.3] , Nicolai J. Birkbak [sup.1] [sup.3] [sup.4] [sup.5] , Rachel Rosenthal [sup.1] [sup.2] [sup.3] , Crispin T. Hiley [sup.1] [sup.3] , Emilia L. Lim [...]

Published
2019
Full Text
View/download PDF

14. 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
Full Text
View/download PDF

16. Neoantigen-directed immune escape in lung cancer evolution

Author

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

Published
2019
Full Text
View/download PDF

18. 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

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

21. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Author

McGranahan, Nicholas, Furness, Andrew J. S., Rosenthal, Rachel, Ramskov, Sofie, Lyngaa, Rikke, Saini, Sunil Kumar, Jamal-Hanjani, Mariam, Wilson, Gareth A., Birkbak, Nicolai J., Hiley, Crispin T., Watkins, Thomas B. K., Shafi, Seema, Murugaesu, Nirupa, Mitter, Richard, Akarca, Ayse U., Linares, Joseph, Marafioti, Teresa, Henry, Jake Y., Van Allen, Eliezer M., Miao, Diana, Schilling, Bastian, Schadendorf, Dirk, Garraway, Levi A., Makarov, Vladimir, Rizvi, Naiyer A., Snyder, Alexandra, Hellmann, Matthew D., Merghoub, Taha, Wolchok, Jedd D., Shukla, Sachet A., Wu, Catherine J., Peggs, Karl S., Chan, Timothy A., Hadrup, Sine R., Quezada, Sergio A., and Swanton, Charles

Published
2016

22. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author

Ng, Kevin W, Boumelha, Jesse, Enfield, Katey SS, Almagro, Jorge, Cha, Hongui, Pich, Oriol, Karasaki, Takahiro, Moore, David A, Salgado, Roberto, Sivakumar, Monica, Young, George, Molina-Arcas, Miriam, de Carné Trécesson, Sophie, Anastasiou, Panayiotis, Fendler, Annika, Au, Lewis, Shepherd, Scott TC, Martínez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Watkins, Thomas BK, Kim, Hyemin, Shim, Seohee, Faulkner, Nikhil, Attig, Jan, Veeriah, Selvaraju, Magno, Neil, Ward, Sophia, Frankell, Alexander M, Al Bakir, Maise, Lim, Emilia L, Hill, Mark S, Wilson, Gareth A, Cook, Daniel E, Birkbak, Nicolai J, Behrens, Axel, Yousaf, Nadia, Popat, Sanjay, Hackshaw, Allan, Consortium, TRACERx, Consortium, CAPTURE, Hiley, Crispin T, Litchfield, Kevin, McGranahan, Nicholas, Jamal-Hanjani, Mariam, Larkin, James, Lee, Se-Hoon, Turajlic, Samra, Swanton, Charles, Downward, Julian, and Kassiotis, George

Subjects
Model organisms, Lung Neoplasms, Immunology, Gene Expression, Adenocarcinoma of Lung, Infectious Disease, Antibodies, Cohort Studies, Mice, Signalling & Oncogenes, Ecology,Evolution & Ethology, Carcinoma, Non-Small-Cell Lung, Tumor Microenvironment, Animals, Humans, Lung, Computational & Systems Biology, Chemical Biology & High Throughput, B-Lymphocytes, Human Biology & Physiology, Stem Cells, FOS: Clinical medicine, Endogenous Retroviruses, Genome Integrity & Repair, Cell Biology, Tumour Biology, Disease Models, Animal, Cell Cycle & Chromosomes, Immunotherapy, Genetics & Genomics
Abstract

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023
Full Text
View/download PDF

24. Abstract 6113: Spatially resolved biomarker detection on single cells in TRACERx using multiplex imaging

Author

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

Published
2022
Full Text
View/download PDF

25. Abstract 645: Heterogeneity of immunotherapy biomarkers in the TRACERx non-small cell lung cancer multi-region lung cancer cohort study

Author

Hiley, Crispin T., primary, Litchfield, Kevin, additional, Pich, Oriol, additional, Moore, David, additional, Naceur-Lombardelli, Cristina, additional, Veeriah, Selvaraju, additional, Bakir, Maise Al, additional, Summan, Simranpreet, additional, Grigoriadis, Kristiana, additional, Ruiz, Carlos Martinez, additional, Puttick, Clare, additional, Enfield, Katey, additional, Ward, Sophia, additional, Frankell, Alexander, additional, Biswas, Dhruva, additional, Rosenthal, Rachel, additional, Birkbak, Nicolai J., additional, Jamal-Hanjani, Mariam, additional, McGranahan, Nicholas, additional, Swanton, Charles, additional, and Consortium, TRACERx, additional

Published
2022
Full Text
View/download PDF

26. Abstract 1394: Pervasive allele specific transcriptional repression of the class I and II HLA genes in TRACERx non-small cell lung cancer

Author

Puttick, Clare, primary, Pich, Oriol, additional, Leung, Michelle, additional, Martinez-Ruiz, Carlos, additional, Bentham, Robert, additional, Rosenthal, Rachel, additional, Hessey, Sonya, additional, Black, James R., additional, Lim, Emilia L., additional, Enfield, Katey, additional, Colliver, Emma, additional, Dijkstra, Krijn, additional, Hiley, Crispin T., additional, Karasaki, Takahiro, additional, Huebner, Ariana, additional, Bakir, Maise Al, additional, Watkins, Thomas B., additional, Frankell, Alexander M., additional, Zaccaria, Simone, additional, Jamal-Hanjani, Mariam, additional, McGranahan, Nicholas, additional, and Swanton, Charles, additional

Published
2022
Full Text
View/download PDF

29. TUMOR IMMUNOLOGY: Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Author

McGranahan, Nicholas, Furness, Andrew J.S., Rosenthal, Rachel, Ramskov, Sofie, Lyngaa, Rikke, Saini, Sunil Kumar, Jamal-Hanjani, Mariam, Wilson, Gareth A., Birkbak, Nicolai J., Hiley, Crispin T., Watkins, Thomas B.K., Shafi, Seema, Murugaesu, Nirupa, Mitter, Richard, Akarca, Ayse U., Linares, Joseph, Marafioti, Teresa, Henry, Jake Y., Van Allen, Eliezer M., Miao, Diana, Schilling, Bastian, Schadendorf, Dirk, Garraway, Levi A., Makarov, Vladimir, Rizvi, Naiyer A., Snyder, Alexandra, Hellmann, Matthew D., Merghoub, Taha, Wolchok, Jedd D., Shukla, Sachet A., Wu, Catherine J., Peggs, Karl S., Chan, Timothy A., Hadrup, Sine R., Quezada, Sergio A., and Swanton, Charles

Published
2016
Full Text
View/download PDF

32. Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Author

AbdulJabbar, Khalid, Raza, Shan E. Ahmed, Rosenthal, Rachel, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Akarca, Ayse, Lund, Tom, Moore, David A., Salgado, Roberto, Al Bakir, Maise, Zapata, Luis, Hiley, Crispin T., Officer, Leah, Sereno, Marco, Smith, Claire Rachel, Loi, Sherene, Hackshaw, Allan, Marafioti, Teresa, Quezada, Sergio A., McGranahan, Nicholas, Le Quesne, John, Swanton, Charles, Yuan, Yinyin, Blyth, Kevin G., Dick, Craig, and Kidd, Andrew

Abstract

Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1,2,3,4,5. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort6. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer–stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes.

Published
2020

33. Publisher Correction: A clonal expression biomarker associates with lung cancer mortality

Author

Biswas, Dhruva, Birkbak, Nicolai J., Rosenthal, Rachel, Hiley, Crispin T., Lim, Emilia L., Papp, Krisztian, and Boeing, Stefan

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): Dhruva Biswas [sup.1] [sup.2] [sup.3] , Nicolai J. Birkbak [sup.1] [sup.3] [sup.4] [sup.5] , Rachel Rosenthal [sup.1] [sup.2] [sup.3] , Crispin T. Hiley [sup.1] [sup.3] , Emilia L. Lim [...]

Published
2020
Full Text
View/download PDF

34. Neoantigen directed immune escape in lung cancer evolution

Author

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

35. Abstract 2678: A clonal expression biomarker improves prognostic accuracy: TRACERx lung

Author

Biswas, Dhruva, primary, Birkbak, Nicolai J., additional, Rosenthal, Rachel, additional, Hiley, Crispin T., additional, Lim, Emilia L., additional, Papp, Krisztian, additional, Krzystanek, Marcin, additional, Djureinovic, Dijana, additional, Wu, Yin, additional, Moore, David A., additional, Skrypski, Marcin, additional, Abbosh, Christopher, additional, Bakir, Maise Al, additional, Watkins, Thomas B., additional, Veeriah, Selvaraju, additional, Wilson, Gareth A., additional, Jamal-Hanjani, Mariam, additional, Chinnaiyan, Arul M., additional, Micke, Patrick, additional, Bartek, Jiri, additional, Csabai, Istvan, additional, Szallasi, Zoltan, additional, Herrero, Javier, additional, McGranahan, Nicholas, additional, and Swanton, Charles, additional

Published
2019
Full Text
View/download PDF

36. Association of the imbalance between early and late differentiated intra-tumor CD4 T cells with mutational burden in non-small cell lung cancer.

Author

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

39. 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
Full Text
View/download PDF

40. Tracking the Evolution of Non–Small-Cell Lung Cancer

Author

Jamal-Hanjani, Mariam, primary, Wilson, Gareth A., additional, McGranahan, Nicholas, additional, Birkbak, Nicolai J., additional, Watkins, Thomas B.K., additional, Veeriah, Selvaraju, additional, Shafi, Seema, additional, Johnson, Diana H., additional, Mitter, Richard, additional, Rosenthal, Rachel, additional, Salm, Max, additional, Horswell, Stuart, additional, Escudero, Mickael, additional, Matthews, Nik, additional, Rowan, Andrew, additional, Chambers, Tim, additional, Moore, David A., additional, Turajlic, Samra, additional, Xu, Hang, additional, Lee, Siow-Ming, additional, Forster, Martin D., additional, Ahmad, Tanya, additional, Hiley, Crispin T., additional, Abbosh, Christopher, additional, Falzon, Mary, additional, Borg, Elaine, additional, Marafioti, Teresa, additional, Lawrence, David, additional, Hayward, Martin, additional, Kolvekar, Shyam, additional, Panagiotopoulos, Nikolaos, additional, Janes, Sam M., additional, Thakrar, Ricky, additional, Ahmed, Asia, additional, Blackhall, Fiona, additional, Summers, Yvonne, additional, Shah, Rajesh, additional, Joseph, Leena, additional, Quinn, Anne M., additional, Crosbie, Phil A., additional, Naidu, Babu, additional, Middleton, Gary, additional, Langman, Gerald, additional, Trotter, Simon, additional, Nicolson, Marianne, additional, Remmen, Hardy, additional, Kerr, Keith, additional, Chetty, Mahendran, additional, Gomersall, Lesley, additional, Fennell, Dean A., additional, Nakas, Apostolos, additional, Rathinam, Sridhar, additional, Anand, Girija, additional, Khan, Sajid, additional, Russell, Peter, additional, Ezhil, Veni, additional, Ismail, Babikir, additional, Irvin-Sellers, Melanie, additional, Prakash, Vineet, additional, Lester, Jason F., additional, Kornaszewska, Malgorzata, additional, Attanoos, Richard, additional, Adams, Haydn, additional, Davies, Helen, additional, Dentro, Stefan, additional, Taniere, Philippe, additional, O’Sullivan, Brendan, additional, Lowe, Helen L., additional, Hartley, John A., additional, Iles, Natasha, additional, Bell, Harriet, additional, Ngai, Yenting, additional, Shaw, Jacqui A., additional, Herrero, Javier, additional, Szallasi, Zoltan, additional, Schwarz, Roland F., additional, Stewart, Aengus, additional, Quezada, Sergio A., additional, Le Quesne, John, additional, Van Loo, Peter, additional, Dive, Caroline, additional, Hackshaw, Allan, additional, and Swanton, Charles, additional

Published
2017
Full Text
View/download PDF

41. 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

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
Full Text
View/download PDF

50. Cash for kidneys: right or wrong?

Author

Hiley, Crispin T., Jones, Robert P., and Johnson, R.W.G.

Subjects
Sale of organs, tissues, etc. -- Economic aspects, Sale of organs, tissues, etc. -- Laws, regulations and rules, Donation of organs, tissues, etc. -- Risk factors, Kidneys -- Transplantation, Kidneys -- Economic aspects, Government regulation, Education, Health
Published
2005

Catalog

Books, media, physical & digital resources
See catalog results