Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer
- Author(s)
- Weeden, CE; Gayevskiy, V; Marceaux, C; Batey, D; Tan, T; Yokote, K; Ribera, NT; Clatch, A; Christo, S; Teh, CE; Mitchell, AJ; Trussart, M; Rankin, LC; Obers, A; McDonald, JA; Sutherland, KD; Sharma, VJ; Starkey, G; D'Costa, R; Antippa, P; Leong, T; Steinfort, D; Irving, L; Swanton, C; Gordon, CL; Mackay, LK; Speed, TP; Gray, DHD; Asselin-Labat, ML;
- Journal Title
- Cancer Cell
- Publication Type
- epub ahead of print
- 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.
- Publisher
- Elsevier
- Keywords
- antigen presentation; cancer immunosurveillance; cigarette smoking; immune evasion; immunotherapy; lung cancer; tissue-resident memory T cells; tumor evolution
- Research Division(s)
- Personalised Oncology; Bioinformatics; Immunology; Cancer Biology And Stem Cells
- PubMed ID
- 37086716
- Publisher's Version
- https://doi.org/10.1016/j.ccell.2023.03.019
- Open Access at Publisher's Site
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Creation Date: 2023-05-01 02:16:57
Last Modified: 2023-06-13 01:11:41