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

Clare E Weeden; Velimir Gayevskiy; Claire Marceaux; Daniel Batey; Tania Tan; Kenta Yokote; Nina Tubau Ribera; Allison Clatch; Susan Christo; Charis E Teh; Andrew J Mitchell; Marie Trussart; Lucille Rankin; Andreas Obers; Jackson A McDonald; Kate D Sutherland; Varun J Sharma; Graham Starkey; Rohit D'Costa; Phillip Antippa; Tracy Leong; Daniel Steinfort; Louis Irving; Charles Swanton; Claire L Gordon; Laura K Mackay; Terence P Speed; Daniel H D Gray; Marie-Liesse Asselin-Labat

doi:10.1016/j.ccell.2023.03.019

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

Cancer Cell. 2023 May 8;41(5):837-852.e6. doi: 10.1016/j.ccell.2023.03.019. Epub 2023 Apr 21.

Authors

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: [email protected].
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: [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / metabolism
Humans
Immunologic Memory
Lung
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism
Memory T Cells

Abstract

Publication types

MeSH terms

Grants and funding