Speaker
Description
Cancer–immune co-evolution shapes tumour progression and immunotherapy
response, but quantitatively linking immune selection pressure to genomic intratumour heterogeneity and to the tumour-infiltrating T-cell receptor (TCR) repertoire remains challenging. Central to this challenge is recognising that immune selection drives a dynamic process in which the TCR repertoire both shapes and is shaped by the evolving tumour genomic landscape.
We set out to identify immune evasion signatures in one of the largest sets of TCR repertoires from non-small cell lung cancer (NSCLC). We performed bulk TCR sequencing on multi-region tumour samples from 265 NSCLC patients in the TRACERx 421 cohort, comprising 1.27 million unique TCRα and 2.5 million TCRβ chains.
A conceptual expectation of cancer–immune co-evolution predicts that the number of mutations is correlated with the number of expanded T-cell clones, previously shown in a smaller subset of the cohort \cite{joshi}. Using data analysis alongside an agent-based model of tumour–immune co-evolution, we investigate the contexts in which this relationship holds. The model links mutation accumulation to T-cell clonal expansion and allows us to explore how immune evasion mechanisms, such as MHC loss and checkpoint mediated immune suppression, perturb this relationship \cite{puttick,martinez-ruiz}. The analysis of the TRACERx 421 genomic, transcriptional and TCR repertoire data reveals foundational principles for the relationship between tumour evolution and host immune control.
Bibliography
@article{joshi,
title = {Spatial Heterogeneity of the {{T}} Cell Receptor Repertoire Reflects the Mutational Landscape in Lung Cancer},
author = {Joshi, Kroopa and De Massy, Marc Robert and Ismail, Mazlina and Reading, James L. and Uddin, Imran and Woolston, Annemarie and Hatipoglu, Emine and Oakes, Theres and Rosenthal, Rachel and Peacock, Thomas and Ronel, Tahel and Noursadeghi, Mahdad and Turati, Virginia and Furness, Andrew J. S. and Georgiou, Andrew and Wong, Yien Ning Sophia and Ben Aissa, Assma and Sunderland, Mariana Werner and {Jamal-Hanjani}, Mariam and Veeriah, Selvaraju and Birkbak, Nicolai J. and Wilson, Gareth A. and Hiley, Crispin T. and Ghorani, Ehsan and {Guerra-Assun{\c c}{\~a}o}, Jos{\'e} Afonso and Herrero, Javier and Enver, Tariq and Hadrup, Sine R. and Hackshaw, Allan and Peggs, Karl S. and McGranahan, Nicholas and Swanton, Charles and Quezada, Sergio A. and Chain, Benny and {TRACERx consortium}},
year = 2019,
month = oct,
journal = {Nature Medicine},
volume = {25},
number = {10},
pages = {1549--1559},
doi = {10.1038/s41591-019-0592-2},
}
@article{puttick,
title = {{{MHC}} Hammer Reveals Genetic and Non-Genetic {{HLA}} Disruption in Cancer Evolution},
author = {Puttick, Clare and Jones, Thomas P. and Leung, Michelle M. and {Galvez-Cancino}, Felipe and Liu, Jiali and {Varas-Godoy}, Manuel and Rowan, Andrew and Pich, Oriol and {Martinez-Ruiz}, Carlos and Bentham, Robert and Dijkstra, Krijn K. and Black, James R. M. and Rosenthal, Rachel and Kanu, Nnennaya and Litchfield, Kevin and Salgado, Roberto and Moore, David A. and Van Loo, Peter and {Jamal-Hanjani}, Mariam and Quezada, Sergio A. and {TRACERx Consortium} and Cheyne, Heather and Khalil, Mohammed and Richardson, Shirley and Cruickshank, Tracey and Lim, Eric and Aerts, Hugo J. W. L. and Kaufmann, Tom L. and Huska, Matthew R. and Naidu, Babu and Wilson, Gareth A. and Rosenthal, Rachel and Rowan, Andrew and Bailey, Chris and Lee, Claudia and Colliver, Emma and Enfield, Katey S. S. and Hill, Mark S. and Angelova, Mihaela and Pich, Oriol and Biswas, Dhruva and Puttick, Clare and Vendramin, Roberto and Murphy, Cian and Zagorulya, Maria and Jones, Thomas P. and Leung, Michelle M. and McGranahan, Nicholas and Castignani, Carla and Cadieux, Elizabeth Larose and Kittel, Jeanette and Haase, Kerstin and Koh, Kexin and Scott, Rachel and Matharu, Gurdeep and Shaw, Jacqui A. and Hackshaw, Allan and Pilotti, Camilla and Leslie, Rachel and Hacker, Anne-Marie and Smith, Sean and Walker, Aoife and Abbosh, Christopher and Richard, Corentin and {Naceur-Lombardelli}, Cristina and {Gimeno-Valiente}, Francisco and Thakkar, Krupa and Sunderland, Mariana Werner and Sivakumar, Monica and Kanu, Nnennaya and Usaite, Ieva and Saghafinia, Sadegh and Veeriah, Selvaraju and Vanloo, Sharon and Mussa, Bushra and Magala, Michalina and Keene, Elizabeth and Lim, Emilia L. and sM Black, James R. and Bakir, Maise Al and Huebner, Ariana and Grigoriadis, Kristiana and Karasaki, Takahiro and Frankell, Alexander M. and Hiley, Crispin T. and Ward, Sophia and Harries, Sian and Lucas, Olivia and Moore, David A. and Birkbak, Nicolai J. and {Mart{\'i}nez-Ruiz}, Carlos and Thol, Kerstin and Bentham, Robert and Liu, Wing Kin and Bunkum, Abigail and Hessey, Sonya and Forster, Martin D. and Lee, Siow Ming and {Jamal-Hanjani}, Mariam and Karagianni, Despoina and Quezada, Sergio A. and Bola, Supreet Kaur and Litchfield, Kevin and Swanton, Charles and Le Quesne, John and AbdulJabbar, Khalid and Veiga, Catarina and Zaccaria, Simone and Tugwood, Jonathan and Dive, Caroline and Szallasi, Zoltan and Diossy, Miklos and Marafioti, Teresa and Borg, Elaine and Falzon, Mary and Khiroya, Reena and Van Loo, Peter and Peggs, Karl S. and Price, Gillian and Royle, Gary and {Collins-Fekete}, Charles-Antoine and {Papadatos-Pastos}, Dionysis and Wilson, James and Ahmad, Tanya and Benafif, Sarah and Cave, Judith and Kerr, Keith M. and Watkins, Thomas B. K. and Salgado, Roberto and Procter, Alexander James and Ahmed, Asia and Taylor, Magali N. and Nair, Arjun and Lawrence, David and Patrini, Davide and Lindsay, Colin R. and Blackhall, Fiona H. and Summers, Yvonne and Krebs, Matthew G. and Nye, Emma and Stone, Richard Kevin and Zhang, Hanyun and Nicod, Jerome and Kirk, Alan and Asif, Mo and Bilancia, Rocco and Kostoulas, Nikos and Whiteley, Jennifer and Thomas, Mathew and Patel, Akshay J. and Chuter, David and MacKenzie, Mairead and Schwarz, Roland F. and Kidd, Andrew and Fraioli, Francesco and Ashford, Paul and Kaplar, Zoltan and Demeulemeester, Jonas and Wilson, Claire and Shackcloth, Michael J. and Janes, Sam M. and Navani, Neal and Thakrar, Ricky M. and Leek, Angela and Hodgkinson, Jack Davies and Totton, Nicola and {Paiva-Correia}, Antonio and Beck, Stephan and Tanic, Miljana and Dick, Craig and Robinson, Lily and Russell, Peter and De Sousa, Paulo and Jordan, Simon and Rice, Alexandra and Raubenheimer, Hilgardt and Bhayani, Harshil and Ambrose, Lyn and Devaraj, Anand and Chavan, Hemangi and Begum, Sofina and Buderi, Silviu I. and Kaniu, Daniel and Malima, Mpho and Booth, Sarah and Fernandes, Nadia and Shah, Pratibha and Proli, Chiara and Nicholson, Andrew G. and Boleti, Ekaterini and Hewish, Madeleine and Blyth, Kevin G. and Lester, Jason F. and Chaturvedi, Anshuman and Oliveira, Pedro and Brown, Katherine D. and Carter, Mathew and Magness, Alastair and Weeden, Clare E. and Gr{\"o}nroos, Eva and Goldman, Jacki and Escudero, Mickael and Hobson, Philip and Boeing, Stefan and Denner, Tamara and Barb{`e}, Vittorio and Lu, Wei-Ting and Hill, William and Naito, Yutaka and Ramsden, Zoe and Kassiotis, George and Noorani, Imran and Grapa, Anca and Alzetani, Aiman and Yuan, Yinyin and Pan, Xiaoxi and French, Jack and Gilbert, Kayleigh and Dwornik, Angela and Karamani, Angeliki and Chain, Benny and Pearce, David R. and {G{\'a}lvez-Cancino}, Felip and Stavrou, Georgia and Mastrokalos, Gerasimos-Theodoros and Lowe, Helen L. and Matos, Ignacio Garcia and Reading, James L. and Hartley, John A. and Selvaraju, Kayalvizhi and Chen, Kezhong and Ensell, Leah and Shah, Mansi and Litovchenko, Maria and Pawlik, Piotr and Gamble, Samuel and Ung, Seng Kuong Anakin and Spanswick, Victoria and Wu, Yin and Rane, Jayant K. and {Al-Sawaf}, Othman and Chervova, Olga and Hoogenboom, Emilie Martinoni and Monk, Fleur and Holding, James W. and Choudhary, Junaid and Bhakhri, Kunal and Gorman, Pat and Stephens, Robert C. M. and Pisciella, Maria Chiara and Bandula, Steve and Wong, Yien Ning Sophia and Osman, Aya and Sangha, Mandeesh and Langman, Gerald and Shackleford, Helen and Djearaman, Madava and Middleton, Gary and Chee, Serena and Georg, Patricia and Bajaj, Amrita and Nakas, Apostolos and {Sodha-Ramdeen}, Azmina and Tufail, Mohamad and Scotland, Molly and Boyles, Rebecca and Rathinam, Sridhar and Marrone, Domenic and Dulloo, Sean and Fennell, Dean A. and Danson, Sarah and Smith, Elaine and Fontaine, Eustace and Granato, Felice and Novasio, Juliette and Rammohan, Kendadai and Joseph, Leena and Bishop, Paul and Shah, Rajesh and Joshi, Vijay and Crosbie, Philip and Swanton, Charles and McGranahan, Nicholas},
year = {2024},
journal = {Nature Genetics},
volume = {56},
number = {10},
pages = {2121--2131},
doi = {10.1038/s41588-024-01883-8},
}
@article{martinez-ruiz,
title = {Genomic--Transcriptomic Evolution in Lung Cancer and Metastasis},
author = {{Mart{\'i}nez-Ruiz}, Carlos and Black, James R. M. and Puttick, Clare and Hill, Mark S. and Demeulemeester, Jonas and Larose Cadieux, Elizabeth and Thol, Kerstin and Jones, Thomas P. and Veeriah, Selvaraju and {Naceur-Lombardelli}, Cristina and Toncheva, Antonia and Prymas, Paulina and Rowan, Andrew and Ward, Sophia and Cubitt, Laura and Athanasopoulou, Foteini and Pich, Oriol and Karasaki, Takahiro and Moore, David A. and Salgado, Roberto and Colliver, Emma and Castignani, Carla and Dietzen, Michelle and Huebner, Ariana and Al Bakir, Maise and Tani{\'c}, Miljana and Watkins, Thomas B. K. and Lim, Emilia L. and {Al-Rashed}, Ali M. and Lang, Danny and Clements, James and Cook, Daniel E. and Rosenthal, Rachel and Wilson, Gareth A. and Frankell, Alexander M. and De Carn{\'e} Tr{\'e}cesson, Sophie and East, Philip and Kanu, Nnennaya and Litchfield, Kevin and Birkbak, Nicolai J. and Hackshaw, Allan and Beck, Stephan and Van Loo, Peter and {Jamal-Hanjani}, Mariam and {TRACERx Consortium} and McGranahan, Nicholas and Swanton, Charles and Bakir, Maise Al and Lim, Emilia L. and Frankell, Alexander M. and Litchfield, Kevin and Birkbak, Nicolai J. and Van Loo, Peter and Lester, Jason F. and Bajaj, Amrita and Nakas, Apostolos and {Sodha-Ramdeen}, Azmina and Ang, Keng and Tufail, Mohamad and Chowdhry, Mohammed Fiyaz and Scotland, Molly and Boyles, Rebecca and Rathinam, Sridhar and Wilson, Claire and Marrone, Domenic and Dulloo, Sean and Fennell, Dean A. and Matharu, Gurdeep and Shaw, Jacqui A. and Riley, Joan and Primrose, Lindsay and Boleti, Ekaterini and Cheyne, Heather and Khalil, Mohammed and Richardson, Shirley and Cruickshank, Tracey and Price, Gillian and Kerr, Keith M. and Benafif, Sarah and Gilbert, Kayleigh and Naidu, Babu and Patel, Akshay J. and Osman, Aya and Lacson, Christer and Langman, Gerald and Shackleford, Helen and Djearaman, Madava and Kadiri, Salma and Middleton, Gary and Leek, Angela and Hodgkinson, Jack Davies and Totten, Nicola and Montero, Angeles and Smith, Elaine and Fontaine, Eustace and Granato, Felice and Doran, Helen and Novasio, Juliette and Rammohan, Kendadai and Joseph, Leena and Bishop, Paul and Shah, Rajesh and Moss, Stuart and Joshi, Vijay and Crosbie, Philip and Gomes, Fabio and Brown, Kate and Carter, Mathew and Chaturvedi, Anshuman and Priest, Lynsey and Oliveira, Pedro and Lindsay, Colin R. and Blackhall, Fiona H. and Krebs, Matthew G. and Summers, Yvonne and Clipson, Alexandra and Tugwood, Jonathan and Kerr, Alastair and Rothwell, Dominic G. and Kilgour, Elaine and Dive, Caroline and Aerts, Hugo J. W. L. and Schwarz, Roland F. and Kaufmann, Tom L. and Szallasi, Zoltan and Kisistok, Judit and Sokac, Mateo and Diossy, Miklos and Bunkum, Abigail and Stewart, Aengus and Magness, Alastair and Karamani, Angeliki and Chain, Benny and Campbell, Brittany B. and Bailey, Chris and Abbosh, Christopher and Weeden, Clare E. and Lee, Claudia and Richard, Corentin and Hiley, Crispin T. and Pearce, David R. and Karagianni, Despoina and Biswas, Dhruva and Levi, Dina and Hoxha, Elena and Nye, Emma and Gr{\"o}nroos, Eva and {G{\'a}lvez-Cancino}, Felip and {Gimeno-Valiente}, Francisco and Kassiotis, George and Stavrou, Georgia and Mastrokalos, Gerasimos and Zhai, Haoran and Lowe, Helen L. and Matos, Ignacio Garcia and Goldman, Jacki and Reading, James L. and Herrero, Javier and Rane, Jayant K. and Nicod, Jerome and Lam, Jie Min and Hartley, John A. and Peggs, Karl S. and Enfield, Katey S. S. and Selvaraju, Kayalvizhi and Ng, Kevin W. and Chen, Kezhong and Dijkstra, Krijn and Grigoriadis, Kristiana and Thakkar, Krupa and Ensell, Leah and Shah, Mansi and Duran, Marcos Vasquez and Litovchenko, Maria and Sunderland, Mariana Werner and Leung, Michelle and Escudero, Mickael and Angelova, Mihaela and Sivakumar, Monica and Chervova, Olga and Lucas, Olivia and {Al-Sawaf}, Othman and Hobson, Philip and Pawlik, Piotr and Stone, Richard Kevin and Bentham, Robert and Hynds, Robert E. and Vendramin, Roberto and Saghafinia, Sadegh and L{\'o}pez, Saioa and Gamble, Samuel and Ung, Seng Kuong Anakin and Quezada, Sergio A. and Vanloo, Sharon and Zaccaria, Simone and Hessey, Sonya and Boeing, Stefan and Bola, Supreet Kaur and Denner, Tamara and Marafioti, Teresa and Mourikis, Thanos P. and Spanswick, Victoria and Barb{`e}, Vittorio and Lu, Wei-Ting and Hill, William and Liu, Wing Kin and Wu, Yin and Naito, Yutaka and Ramsden, Zoe and Veiga, Catarina and Royle, Gary and {Collins-Fekete}, Charles-Antoine and Fraioli, Francesco and Ashford, Paul and Clark, Tristan and Forster, Martin D. and Lee, Siow Ming and Borg, Elaine and Falzon, Mary and {Papadatos-Pastos}, Dionysis and Wilson, James and Ahmad, Tanya and Procter, Alexander James and Ahmed, Asia and Taylor, Magali N. and Nair, Arjun and Lawrence, David and Patrini, Davide and Navani, Neal and Thakrar, Ricky M. and Janes, Sam M. and Hoogenboom, Emilie Martinoni and Monk, Fleur and Holding, James W. and Choudhary, Junaid and Bhakhri, Kunal and Scarci, Marco and Hayward, Martin and Panagiotopoulos, Nikolaos and Gorman, Pat and Khiroya, Reena and Stephens, Robert C. M. and Wong, Yien Ning Sophia and Bandula, Steve and Sharp, Abigail and Smith, Sean and Gower, Nicole and Dhanda, Harjot Kaur and Chan, Kitty and Pilotti, Camilla and Leslie, Rachel and Grapa, Anca and Zhang, Hanyun and AbdulJabbar, Khalid and Pan, Xiaoxi and Yuan, Yinyin and Chuter, David and MacKenzie, Mairead and Chee, Serena and Alzetani, Aiman and Cave, Judith and Scarlett, Lydia and Richards, Jennifer and Ingram, Papawadee and Austin, Silvia and Lim, Eric and De Sousa, Paulo and Jordan, Simon and Rice, Alexandra and Raubenheimer, Hilgardt and Bhayani, Harshil and Ambrose, Lyn and Devaraj, Anand and Chavan, Hema and Begum, Sofina and Buderi, Silviu I. and Kaniu, Daniel and Malima, Mpho and Booth, Sarah and Nicholson, Andrew G. and Fernandes, Nadia and Shah, Pratibha and Proli, Chiara and Hewish, Madeleine and Danson, Sarah and Shackcloth, Michael J. and Robinson, Lily and Russell, Peter and Blyth, Kevin G. and Dick, Craig and Le Quesne, John and Kirk, Alan and Asif, Mo and Bilancia, Rocco and Kostoulas, Nikos and Thomas, Mathew and Swanton, Charles and McGranahan, Nicholas},
year = {2023},
journal = {Nature},
volume = {616},
number = {7957},
pages = {543--552},
publisher = {Nature Publishing Group},
doi = {10.1038/s41586-023-05706-4},
keywords = {Cancer evolution,Priority Read,To read,TracerX},
}
