Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Clare E Weeden¹, Velimir Gayevskiy¹, Claire Marceaux¹, Daniel Batey², Tania Tan³, Kenta Yokote², Nina Tubau Ribera⁴, Allison Clatch⁵, Susan Christo⁵, Charis E Teh⁶, Andrew J Mitchell⁷, Marie Trussart⁸, Lucille Rankin⁶, Andreas Obers⁵, Jackson A McDonald⁹, Kate D Sutherland⁹, Varun J Sharma¹⁰, Graham Starkey¹¹, Rohit D'Costa¹², Phillip Antippa¹³, Tracy Leong¹⁴, Daniel Steinfort¹⁵, Louis Irving¹⁵, Charles Swanton¹⁶, Claire L Gordon¹⁷, Laura K Mackay⁵, Terence P Speed¹⁸, Daniel H D Gray¹⁹, Marie-Liesse Asselin-Labat²⁰

Affiliations

¹ Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia.
² Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
³ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁴ Advanced Technology and Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁵ Department of Microbiology and Immunology, the University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.
⁶ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia.
⁷ Materials Characterisation and Fabrication Platform, Department of Chemical Engineering, the University of Melbourne, Parkville, VIC, Australia.
⁸ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁹ ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia.
¹⁰ Department of Surgery, the University of Melbourne, Parkville, VIC, Australia; Liver and Intestinal Transplant Unit, Austin Health, Heidelberg, VIC, Australia; Department of Cardiothoracic Surgery, Austin Health, Heidelberg, VIC, Australia.
¹¹ Department of Surgery, the University of Melbourne, Parkville, VIC, Australia; Liver and Intestinal Transplant Unit, Austin Health, Heidelberg, VIC, Australia.
¹² DonateLife Victoria, Carlton, VIC, Australia; Department of Intensive Care Medicine, Melbourne Health, Melbourne, VIC, Australia.
¹³ Department of Surgery, the University of Melbourne, Parkville, VIC, Australia; The Royal Melbourne Hospital, Parkville, VIC, Australia.
¹⁴ Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia; Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, VIC, Australia.
¹⁵ Department of Medicine, the University of Melbourne, Parkville, VIC, Australia; The Royal Melbourne Hospital, Parkville, VIC, Australia.
¹⁶ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, UK; University College London Hospitals, London, UK.
¹⁷ Department of Microbiology and Immunology, the University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia; Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia; North Eastern Public Health Unit, Austin Health, Heidelberg, VIC, Australia.
¹⁸ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; School of Mathematics and Statistics, the University of Melbourne, Parkville, VIC, Australia.
¹⁹ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia. Electronic address: dgray@wehi.edu.au.
²⁰ Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia. Electronic address: labat@wehi.edu.au.

PMID: 37086716
DOI: 10.1016/j.ccell.2023.03.019

Free article

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Clare E Weeden et al. Cancer Cell. 2023.

Free article

. 2023 May 8;41(5):837-852.e6.

doi: 10.1016/j.ccell.2023.03.019. Epub 2023 Apr 21.

Authors

Affiliations

¹ Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia.
² Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
³ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁴ Advanced Technology and Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁵ Department of Microbiology and Immunology, the University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.
⁶ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia.
⁷ Materials Characterisation and Fabrication Platform, Department of Chemical Engineering, the University of Melbourne, Parkville, VIC, Australia.
⁸ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁹ ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia.
¹⁰ Department of Surgery, the University of Melbourne, Parkville, VIC, Australia; Liver and Intestinal Transplant Unit, Austin Health, Heidelberg, VIC, Australia; Department of Cardiothoracic Surgery, Austin Health, Heidelberg, VIC, Australia.
¹¹ Department of Surgery, the University of Melbourne, Parkville, VIC, Australia; Liver and Intestinal Transplant Unit, Austin Health, Heidelberg, VIC, Australia.
¹² DonateLife Victoria, Carlton, VIC, Australia; Department of Intensive Care Medicine, Melbourne Health, Melbourne, VIC, Australia.
¹³ Department of Surgery, the University of Melbourne, Parkville, VIC, Australia; The Royal Melbourne Hospital, Parkville, VIC, Australia.
¹⁴ Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia; Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, VIC, Australia.
¹⁵ Department of Medicine, the University of Melbourne, Parkville, VIC, Australia; The Royal Melbourne Hospital, Parkville, VIC, Australia.
¹⁶ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, UK; University College London Hospitals, London, UK.
¹⁷ Department of Microbiology and Immunology, the University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia; Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia; North Eastern Public Health Unit, Austin Health, Heidelberg, VIC, Australia.
¹⁸ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; School of Mathematics and Statistics, the University of Melbourne, Parkville, VIC, Australia.
¹⁹ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia. Electronic address: dgray@wehi.edu.au.
²⁰ Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia. Electronic address: labat@wehi.edu.au.

PMID: 37086716
DOI: 10.1016/j.ccell.2023.03.019

Abstract

Tissue-resident memory T (T_RM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts T_RM activation and whether T_RM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a T_RM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander T_RM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced T_RM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

Keywords: antigen presentation; cancer immunosurveillance; cigarette smoking; immune evasion; immunotherapy; lung cancer; tissue-resident memory T cells; tumor evolution.

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Conflict of interest statement

Declaration of interests C.S. acknowledges grant support from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Pfizer, Roche-Ventana, Invitae (previously Archer Dx Inc–collaboration in minimal residual disease sequencing technologies), and Ono Pharmaceutical. C.S. is an AstraZeneca Advisory Board member and Chief Investigator for the AZ MeRmaiD 1 and 2 clinical trials and is also Co-Chief Investigator of the NHS Galleri trial funded by GRAIL and a paid member of GRAIL’s SAB. He receives consultant fees from Achilles Therapeutics (also SAB member), Bicycle Therapeutics (also a SAB member), Genentech, Medicxi, Roche Innovation Centre– Shanghai, Metabomed (until July 2022), and the Sarah Cannon Research Institute. He had stock options in Apogen Biotechnologies and GRAIL until June 2021, and currently has stock options in Epic Bioscience, Bicycle Therapeutics, and has stock options and is co-founder of Achilles Therapeutics. C.S. is an inventor on a European patent application relating to assay technology to detect tumour recurrence (PCT/GB2017/053289), the patent has been licensed to commercial entities, and under his terms of employment, C.S. is due a revenue share of any revenue generated from such licence(s). C.S. holds patents relating to targeting neoantigens (PCT/EP2016/059401), identifying patient response to immune checkpoint blockade (PCT/EP2016/071471), determining HLA LOH (PCT/GB2018/052004), predicting survival rates of patients with cancer (PCT/GB2020/050221), identifying patients who respond to cancer treatment (PCT/GB2018/051912), a US patent relating to detecting tumour mutations (PCT/US2017/28013), methods for lung cancer detection (US20190106751A1) and both a European and US patent related to identifying insertion/deletion mutation targets (PCT/GB2018/051892) and is co-inventor to a patent application to determine methods and systems for tumour monitoring (PCT/EP2022/077987). C.S has received honoraria from Amgen, AstraZeneca, Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol Myers Squibb, Illumina, and Roche-Ventana.

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Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Affiliations

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Research Materials