Subclonal immune evasion in non-small cell lung cancer

Krijn K Dijkstra¹, Roberto Vendramin², Despoina Karagianni³, Maartje Witsen⁴, Felipe Gálvez-Cancino⁵, Mark S Hill⁶, Kane A Foster⁷, Vittorio Barbè⁶, Mihaela Angelova⁸, Robert E Hynds⁹, David R Pearce⁶, Carlos Martínez-Ruiz⁶, James R M Black⁶, Ariana Huebner⁶, Oriol Pich⁶, Andrew Rowan⁸, Marcellus Augustine¹⁰, Clare Puttick¹¹, David A Moore¹², Lydia L Liu⁶, Sadegh Saghafinia⁶, Joris van de Haar⁴, Selvaraju Veeriah⁶, Cristina Naceur-Lombardelli⁶, Antonia Toncheva⁶, Supreet Kaur Bola³, Crispin T Hiley⁶, Mariam Jamal-Hanjani¹³, Nicholas McGranahan¹⁴, Kevin Litchfield¹⁵, James L Reading¹⁶, Benny Chain¹⁷; TRACERx consortium; Sergio A Quezada¹⁸, Emile E Voest¹⁹, Charles Swanton²⁰

Collaborators, Affiliations

Collaborators

TRACERx consortium:
Abigail Bunkum, Adam Atkin, Aiman Alzetani, Akshay J Patel, Alan Kirk, Alexander James Procter, Alexander M Frankell, Alexandra Rice, Allan Hackshaw, Amrita Bajaj, Anand Devaraj, Anca Grapa, Andrew G Nicholson, Andrew Kidd, Andrew Rowan, Angela Dwornik, Angela Leek, Angeliki Karamani, Anne-Marie Hacker, Anshuman Chaturvedi, Antonio Paiva-Correia, Aoife Walker, Apostolos Nakas, Ariana Huebner, Arjun Nair, Asia Ahmed, Aya Osman, Azmina Sodha-Ramdeen, Babu Naidu, Benny Chain, Camilla Pilotti, Carla Castignani, Carlos Martínez-Ruiz, Caroline Dive, Catarina Veiga, Charles Swanton, Charles-Antoine Collins-Fekete, Chiara Proli, Chris Bailey, Cian Murphy, Claire Wilson, Clare E Weeden, Clare Puttick, Claudia Lee, Colin R Lindsay, Corentin Richard, Craig Dick, Crispin T Hiley, Cristina Naceur-Lombardelli, Daniel Kaniu, David A Moore, David Chuter, David Lawrence, David R Pearce, Davide Patrini, Dean A Fennell, Despoina Karagianni, Dionysis Papadatos-Pastos, Ekaterini Boleti, Elaine Borg, Elizabeth Keene, Emilia L Lim, Emilie Martinoni Hoogenboom, Emma Colliver, Emma Nye, Eric Lim, Erik Sahai, Eustace Fontaine, Eva Grönroos, Felice Granato, Fiona H Blackhall, Fleur Monk, Francesco Fraioli, Francisco Gimeno-Valiente, Gareth A Wilson, Gary Middleton, Gary Royle, George Kassiotis, Georgia Moth, Georgia Stavrou, Gerald Langman, Gerasimos-Theodoros Mastrokalos, Gillian Price, Gurdeep Matharu, Hanyun Zhang, Harshil Bhayani, Heather Cheyne, Helen L Lowe, Helen Shackleford, Hemangi Chavan, Hilgardt Raubenheimer, Hugo Jwl Aerts, Ieva Usaite, Imran Noorani, Jack Davies Hodgkinson, Jack French, Jacki Goldman, Jacqui A Shaw, James L Reading, James R M Black, James W Holding, James Wilson, Jason F Lester, Jayant K Rane, Jeanette Kittel, Jennifer Whiteley, Jerome Nicod, John A Hartley, John Le Quesne, Jonas Demeulemeester, Jonathan Tugwood, Judith Cave, Juliette Novasio, Junaid Choudhary, Karen Grimes, Karl S Peggs, Katey S S Enfield, Katherine D Brown, Kayalvizhi Selvaraju, Kayleigh Gilbert, Keith M Kerr, Kendadai Rammohan, Kerstin Haase, Kerstin Thol, Kevin G Blyth, Kexin Koh, Khalid AbdulJabbar, Kristiana Grigoriadis, Krupa Thakkar, Kunal Bhakhri, Leah Ensell, Leena Joseph, Lily Robinson, Lucrezia Patruno, Lyn Ambrose, Madava Djearaman, Madeleine Hewish, Magali N Taylor, Mairead MacKenzie, Maise Al Bakir, Mandeesh Sangha, Mansi Shah, Maria Chiara Pisciella, Maria Litovchenko, Maria Zagorulya, Mariam Jamal-Hanjani, Martin D Forster, Mary Falzon, Mathew Carter, Mathew Thomas, Matthew G Krebs, Michael J Shackcloth, Michalina Magala, Michelle M Leung, Mickael Escudero, Mihaela Angelova, Miklos Diossy, Mo Asif, Mohamad Tufail, Mohammed Khalil, Molly Scotland, Monica Sivakumar, Mpho Malima, Nadia Fernandes, Neal Navani, Nicholas McGranahan, Nicola Totton, Nicolai J Birkbak, Nikos Kostoulas, Nnennaya Kanu, Olivia Lucas, Oriol Pich, Pat Gorman, Patricia Georg, Paul Ashford, Paul Bishop, Paulo De Sousa, Pedro Oliveira, Peter Russell, Peter Van Loo, Philip Crosbie, Philip Hobson, Piotr Pawlik, Pratibha Shah, Rachel Rosenthal, Rebecca Boyles, Reena Khiroya, Richard Kevin Stone, Ricky M Thakrar, Rija Zaidi, Robert Bentham, Robert C M Stephens, Roberto Salgado, Roberto Vendramin, Rocco Bilancia, Roland F Schwarz, Sadegh Saghafinia, Salomey Kellet, Sam M Janes, Samuel Gamble, Sara Waplington, Sarah Benafif, Sarah Booth, Sarah Danson, Sean Dulloo, Selvaraju Veeriah, Seng Kuong Anakin Ung, Serena Chee, Sergio A Quezada, Sharon Vanloo, Shirley Richardson, Sian Harries, Silviu I Buderi, Simon Jordan, Simone Zaccaria, Siow Ming Lee, Sofina Begum, Sonya Hessey, Sophia Ward, Sridhar Rathinam, Stefan Boeing, Stephan Beck, Steve Bandula, Supreet Kaur Bola, Takahiro Karasaki, Tamara Denner, Tanya Ahmad, Teresa Marafioti, Theepan Visakan, Thomas B K Watkins, Thomas Patrick Jones, Tom L Kaufmann, Tracey Cruickshank, Victoria Spanswick, Vijay Joshi, Vittorio Barbè, Wei-Ting Lu, William Hill, Wing Kin Liu, Xiaoxi Pan, Yien Ning Sophia Wong, Yin Wu, Yinyin Yuan, Yutaka Naito, Yvonne Summers, Zainab Kalokoh, Zoe Ramsden, Zoltan Kaplar, Zoltan Szallasi

Affiliations

¹ Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Oncode Institute, Utrecht, the Netherlands. Electronic address: k.dijkstra@nki.nl.
² Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Tumor ImmunoGenomics and Immunosurveillance Laboratory, University College London Cancer Institute, University College London, London, UK.
³ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK.
⁴ Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
⁵ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK; Immune Regulation Laboratory, Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
⁶ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
⁷ Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK.
⁸ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
⁹ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Epithelial Cell Biology in ENT Research (EpiCENTR) Group, Developmental Biology and Cancer Department, Great Ormond Street UCL Institute of Child Health, University College London, London, UK.
¹⁰ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Tumor ImmunoGenomics and Immunosurveillance Laboratory, University College London Cancer Institute, University College London, London, UK; Division of Medicine, University College London, London, UK.
¹¹ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
¹² Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Department of Cellular Pathology, University College London Hospital, London, UK.
¹³ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK; Department of Medical Oncology, University College London Hospitals, London, UK.
¹⁴ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
¹⁵ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Tumor ImmunoGenomics and Immunosurveillance Laboratory, University College London Cancer Institute, University College London, London, UK.
¹⁶ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, London, UK.
¹⁷ University College London Cancer Institute, London, UK; Division of Infection and Immunity, University College London, London, UK.
¹⁸ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK. Electronic address: s.quezada@ucl.ac.uk.
¹⁹ Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, Utrecht, the Netherlands. Electronic address: e.voest@nki.nl.
²⁰ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Department of Medical Oncology, University College London Hospitals, London, UK. Electronic address: charles.swanton@crick.ac.uk.

PMID: 40614739
DOI: 10.1016/j.ccell.2025.06.012

Free article

Subclonal immune evasion in non-small cell lung cancer

Krijn K Dijkstra et al. Cancer Cell. 2025.

Free article

. 2025 Jul 1:S1535-6108(25)00262-4.

doi: 10.1016/j.ccell.2025.06.012. Online ahead of print.

Authors

Collaborators

TRACERx consortium:
Abigail Bunkum, Adam Atkin, Aiman Alzetani, Akshay J Patel, Alan Kirk, Alexander James Procter, Alexander M Frankell, Alexandra Rice, Allan Hackshaw, Amrita Bajaj, Anand Devaraj, Anca Grapa, Andrew G Nicholson, Andrew Kidd, Andrew Rowan, Angela Dwornik, Angela Leek, Angeliki Karamani, Anne-Marie Hacker, Anshuman Chaturvedi, Antonio Paiva-Correia, Aoife Walker, Apostolos Nakas, Ariana Huebner, Arjun Nair, Asia Ahmed, Aya Osman, Azmina Sodha-Ramdeen, Babu Naidu, Benny Chain, Camilla Pilotti, Carla Castignani, Carlos Martínez-Ruiz, Caroline Dive, Catarina Veiga, Charles Swanton, Charles-Antoine Collins-Fekete, Chiara Proli, Chris Bailey, Cian Murphy, Claire Wilson, Clare E Weeden, Clare Puttick, Claudia Lee, Colin R Lindsay, Corentin Richard, Craig Dick, Crispin T Hiley, Cristina Naceur-Lombardelli, Daniel Kaniu, David A Moore, David Chuter, David Lawrence, David R Pearce, Davide Patrini, Dean A Fennell, Despoina Karagianni, Dionysis Papadatos-Pastos, Ekaterini Boleti, Elaine Borg, Elizabeth Keene, Emilia L Lim, Emilie Martinoni Hoogenboom, Emma Colliver, Emma Nye, Eric Lim, Erik Sahai, Eustace Fontaine, Eva Grönroos, Felice Granato, Fiona H Blackhall, Fleur Monk, Francesco Fraioli, Francisco Gimeno-Valiente, Gareth A Wilson, Gary Middleton, Gary Royle, George Kassiotis, Georgia Moth, Georgia Stavrou, Gerald Langman, Gerasimos-Theodoros Mastrokalos, Gillian Price, Gurdeep Matharu, Hanyun Zhang, Harshil Bhayani, Heather Cheyne, Helen L Lowe, Helen Shackleford, Hemangi Chavan, Hilgardt Raubenheimer, Hugo Jwl Aerts, Ieva Usaite, Imran Noorani, Jack Davies Hodgkinson, Jack French, Jacki Goldman, Jacqui A Shaw, James L Reading, James R M Black, James W Holding, James Wilson, Jason F Lester, Jayant K Rane, Jeanette Kittel, Jennifer Whiteley, Jerome Nicod, John A Hartley, John Le Quesne, Jonas Demeulemeester, Jonathan Tugwood, Judith Cave, Juliette Novasio, Junaid Choudhary, Karen Grimes, Karl S Peggs, Katey S S Enfield, Katherine D Brown, Kayalvizhi Selvaraju, Kayleigh Gilbert, Keith M Kerr, Kendadai Rammohan, Kerstin Haase, Kerstin Thol, Kevin G Blyth, Kexin Koh, Khalid AbdulJabbar, Kristiana Grigoriadis, Krupa Thakkar, Kunal Bhakhri, Leah Ensell, Leena Joseph, Lily Robinson, Lucrezia Patruno, Lyn Ambrose, Madava Djearaman, Madeleine Hewish, Magali N Taylor, Mairead MacKenzie, Maise Al Bakir, Mandeesh Sangha, Mansi Shah, Maria Chiara Pisciella, Maria Litovchenko, Maria Zagorulya, Mariam Jamal-Hanjani, Martin D Forster, Mary Falzon, Mathew Carter, Mathew Thomas, Matthew G Krebs, Michael J Shackcloth, Michalina Magala, Michelle M Leung, Mickael Escudero, Mihaela Angelova, Miklos Diossy, Mo Asif, Mohamad Tufail, Mohammed Khalil, Molly Scotland, Monica Sivakumar, Mpho Malima, Nadia Fernandes, Neal Navani, Nicholas McGranahan, Nicola Totton, Nicolai J Birkbak, Nikos Kostoulas, Nnennaya Kanu, Olivia Lucas, Oriol Pich, Pat Gorman, Patricia Georg, Paul Ashford, Paul Bishop, Paulo De Sousa, Pedro Oliveira, Peter Russell, Peter Van Loo, Philip Crosbie, Philip Hobson, Piotr Pawlik, Pratibha Shah, Rachel Rosenthal, Rebecca Boyles, Reena Khiroya, Richard Kevin Stone, Ricky M Thakrar, Rija Zaidi, Robert Bentham, Robert C M Stephens, Roberto Salgado, Roberto Vendramin, Rocco Bilancia, Roland F Schwarz, Sadegh Saghafinia, Salomey Kellet, Sam M Janes, Samuel Gamble, Sara Waplington, Sarah Benafif, Sarah Booth, Sarah Danson, Sean Dulloo, Selvaraju Veeriah, Seng Kuong Anakin Ung, Serena Chee, Sergio A Quezada, Sharon Vanloo, Shirley Richardson, Sian Harries, Silviu I Buderi, Simon Jordan, Simone Zaccaria, Siow Ming Lee, Sofina Begum, Sonya Hessey, Sophia Ward, Sridhar Rathinam, Stefan Boeing, Stephan Beck, Steve Bandula, Supreet Kaur Bola, Takahiro Karasaki, Tamara Denner, Tanya Ahmad, Teresa Marafioti, Theepan Visakan, Thomas B K Watkins, Thomas Patrick Jones, Tom L Kaufmann, Tracey Cruickshank, Victoria Spanswick, Vijay Joshi, Vittorio Barbè, Wei-Ting Lu, William Hill, Wing Kin Liu, Xiaoxi Pan, Yien Ning Sophia Wong, Yin Wu, Yinyin Yuan, Yutaka Naito, Yvonne Summers, Zainab Kalokoh, Zoe Ramsden, Zoltan Kaplar, Zoltan Szallasi

Affiliations

¹ Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Oncode Institute, Utrecht, the Netherlands. Electronic address: k.dijkstra@nki.nl.
² Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Tumor ImmunoGenomics and Immunosurveillance Laboratory, University College London Cancer Institute, University College London, London, UK.
³ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK.
⁴ Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
⁵ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK; Immune Regulation Laboratory, Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
⁶ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
⁷ Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK.
⁸ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
⁹ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Epithelial Cell Biology in ENT Research (EpiCENTR) Group, Developmental Biology and Cancer Department, Great Ormond Street UCL Institute of Child Health, University College London, London, UK.
¹⁰ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Tumor ImmunoGenomics and Immunosurveillance Laboratory, University College London Cancer Institute, University College London, London, UK; Division of Medicine, University College London, London, UK.
¹¹ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
¹² Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Department of Cellular Pathology, University College London Hospital, London, UK.
¹³ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK; Department of Medical Oncology, University College London Hospitals, London, UK.
¹⁴ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
¹⁵ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Tumor ImmunoGenomics and Immunosurveillance Laboratory, University College London Cancer Institute, University College London, London, UK.
¹⁶ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, London, UK.
¹⁷ University College London Cancer Institute, London, UK; Division of Infection and Immunity, University College London, London, UK.
¹⁸ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Immunology Unit, Immune Regulation and Tumor Immunotherapy Group, Research Department of Haematology, University College London Cancer Institute, London, UK. Electronic address: s.quezada@ucl.ac.uk.
¹⁹ Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, Utrecht, the Netherlands. Electronic address: e.voest@nki.nl.
²⁰ Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Department of Medical Oncology, University College London Hospitals, London, UK. Electronic address: charles.swanton@crick.ac.uk.

PMID: 40614739
DOI: 10.1016/j.ccell.2025.06.012

Abstract

Cancers rarely respond completely to immunotherapy. While tumors consist of multiple genetically distinct clones, whether this affects the potential for immune escape remains unclear due to an inability to isolate and propagate individual subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived organoid - T cell co-culture platform that allows the functional analysis of subclonal immune escape at single clone resolution. We establish organoid lines from 11 separate tumor regions from three patients, followed by isolation of 81 individual clonal sublines. Co-culture with tumor infiltrating lymphocytes (TIL) or natural killer (NK) cells reveals cancer-intrinsic and subclonal immune escape in all 3 patients. Immune evading subclones represent genetically distinct lineages with a unique evolutionary history. This indicates that immune evading and non-evading subclones can be isolated from the same tumor, suggesting that subclonal tumor evolution directly affects immune escape.

Keywords: T cell; cancer evolution; immune escape; immune evasion; immunosurveillance; immunotherapy; intratumor heterogeneity; non-small cell lung cancer; organoids; tumor evolution; tumor immunology.

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Conflict of interest statement

Declaration of interests K.K.D. provided consultancy services to Achilles Therapeutics UK Ltd. R.V. declares research funding from CRUK TDL–Ono–LifeArc alliance and Genesis Therapeutics. K.L. has a patent on indel burden and CPI response pending and speaker fees from Roche tissue diagnostics, research funding from CRUK TDL–Ono–LifeArc alliance, Genesis Therapeutics, and consulting roles with Ellipses Pharma, Monopteros, Tempus, Saga Diagnostics, and Kynos Therapeutics. K.L. is a current employee of Isomorphic Labs. C.P. holds a patent pending in determining HLA disruption (PCT/EP2023/059039). J.v.d.H. received research funding from Sanofi S.A. outside this work. D.A.M. reports speaker fees from AstraZeneca, Eli Lilly, BMS and Takeda, consultancy fees from AstraZeneca, Thermo Fisher, Takeda, Amgen, Janssen, MIM Software, Bristol-Myers Squibb, and Eli Lilly and has received educational support from Takeda and Amgen. C.T.H. received speaker fees from AstraZeneca and Merck, research funding from Roche, Astra Zeneca and UCLH NIHR BRC, and has a paid advisory role for GenesisCareUK. E.E.V. is founder and current member of the supervisory board of the Hartwig Medical Foundation, independent non-executive director of Sanofi, co-founder of Mosaic Therapeutics, and board member and founder of the Center for Personalized Cancer Treatment. He has received clinical study grants from Amgen, AstraZeneca, BI, BMS, Clovis, Eli Lilly, GSK, Ipsen, MSD, Novartis, Pfizer, Roche, and Sanofi. J.L.R. reports speaker fees from Boehringer Ingelheim and GlaxoSmithKline, consults for Achilles Therapeutics Ltd and has filed patents for T cell driven cancer early detection (PCT/EP2023/076521 and PCT/EP2023/076511). M.J.-H. has consulted for Astex Pharmaceuticals, Pfizer and Achilles Therapeutics, and is a member of the Achilles Therapeutics Scientific Advisory Board and Steering Committee, has received speaker honoraria from Pfizer, Astex Pharmaceuticals, Oslo Cancer Cluster, Bristol Myers Squibb, Genentech and GenesisCare. M.J.-H is listed as a co-inventor on a European patent application relating to methods to detect lung cancer (PCT/US2017/028013), this patent has been licensed to commercial entities and, under terms of employment, M.J.-H. is due a share of any revenue generated from such license(s), and is also listed as a co-inventor on the GB priority patent application (GB2400424.4) with title: Treatment and Prevention of Lung Cancer. N.M. has stock options in and has consulted for Achilles Therapeutics and holds a European patent in determining HLA LOH (PCT/GB2018/052004), a patent pending in determining HLA disruption (PCT/EP2023/059039), and is a co-inventor to a patent to identify responders to cancer treatment (PCT/GB2018/051912). S.A.Q. is a founder, CSO, and holds stock options of Achilles Therapeutics, a company developing personalized T cell therapies targeting clonal neoantigens. C.S. acknowledges grants from AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Pfizer, Roche-Ventana, Invitae (previously Archer Dx Inc - collaboration in minimal residual disease sequencing technologies), Ono Pharmaceutical, and Personalis. He is Chief Investigator for the AZ MeRmaiD 1 and 2 clinical trials and is the Steering Committee Chair. He is also Co-Chief Investigator of the NHS Galleri trial funded by GRAIL and a paid member of GRAIL’s Scientific Advisory Board. He receives consultant fees from Achilles Therapeutics (also SAB member), Bicycle Therapeutics (also an SAB member and Chair of the Clinical Advisory Group), Genentech, Medicxi, Novartis, China Innovation Centre of Roche (CICoR) formerly Roche Innovation Centre – Shanghai, Metabomed (until July 2022), Relay Therapeutics SAB member, Saga Diagnostics SAB member and the Sarah Cannon Research Institute. C.S. has received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Illumina, MSD, Novartis, Pfizer, and Roche-Ventana. C.S. has previously held stock options in Apogen Biotechnologies and GRAIL, and currently has stock options in Epic Bioscience, Bicycle Therapeutics, Relay Therapeutics, and has stock options and is co-founder of Achilles Therapeutics. C.S. declares a patent application for methods to detect lung cancer (PCT/US2017/028013); targeting neoantigens (PCT/EP2016/059401); identifying patient response to immune checkpoint blockade (PCT/EP2016/071471); methods for lung cancer detection (US20190106751A1); identifying patients who respond to cancer treatment (PCT/GB2018/051912); determining HLA LOH (PCT/GB2018/052004); predicting survival rates of patients with cancer (PCT/GB2020/050221); methods and systems for tumor monitoring (PCT/EP2022/077987); analysis of HLA alleles transcriptional deregulation (PCT/EP2023/059039). C.S. is an inventor on a European patent application (PCT/GB2017/053289) relating to assay technology to detect tumor recurrence. This patent has been licensed to a commercial entity and under their terms of employment C.S. is due a revenue share of any revenue generated from such license(s). C.S. is a Royal Society Napier Research Professor (RSRP∖R∖210001).

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Subclonal immune evasion in non-small cell lung cancer

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Affiliations

Subclonal immune evasion in non-small cell lung cancer

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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