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

Weeden, CE; Gayevskiy, V; Marceaux, C; Batey, D; Tan, T; Yokote, K; Ribera, NT; ... Asselin-Labat, ML; + view all (2023) Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer. Cancer Cell , 41 (5) 837-852.e6. 10.1016/j.ccell.2023.03.019. Green open access

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Abstract

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM 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 TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-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 TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

Type: Article
Title: Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ccell.2023.03.019
Publisher version: https://doi.org/10.1016/j.ccell.2023.03.019
Language: English
Additional information: © 2023 The Author(s). Published by Elsevier Inc. under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/).
Keywords: antigen presentation, cancer immunosurveillance, cigarette smoking, immune evasion, immunotherapy, lung cancer, tissue-resident memory T cells, tumor evolution
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10169809
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