Journal article
Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer
CE Weeden, V Gayevskiy, C Marceaux, D Batey, T Tan, K Yokote, NT Ribera, A Clatch, S Christo, CE Teh, AJ Mitchell, M Trussart, L Rankin, A Obers, JA McDonald, KD Sutherland, VJ Sharma, G Starkey, R D'Costa, P Antippa Show all
Cancer Cell | Published : 2023
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 e..
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Awarded by Breast Cancer Research Foundation
Funding Acknowledgements
We thank Dr. Alexandra Garnham for advice on analyzing CyTOF data, Dr. Alissa Robbins for T cell reagents and CyTOF advice, and Dr. Sarah Best for mouse model advice and critical reading of the manuscript. We thank WEHI facilities including Histology (Emma Pan and Ellen Tsui) , Flow Cytometry (Simon Monard) , and Bioservices (Shannon Oliver, Eren Loza, Keti Florides, Louise Spencer) for expert advice and performing experiments. The MR1 tetramer technology was developed jointly by Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie, and the material was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Mel-bourne. We are grateful to the Victorian Cancer Biobank and all lung cancer patients who participated in this study. We gratefully acknowledge the gener-osity of the organ donor families in providing valuable tissue samples to the Australian Donation and Transplantation Biobank. This work was performed in part at the Materials Characterisation and Fabrication Plat-form (MCFP) at the University of Melbourne under Andrew Mitchell's leadership, and the Victo-rian Node of the Australian National Fabrication Facility (ANFF) , with support from the Victorian Comprehensive Cancer Centre under the Resistance to Tar-geted Therapies Program. The mass cytometry studies were also supported in part by the Australian Cancer Research Foundation. C.E.W. is supported by a Lung foundation Australia/Deep Manchanda Early Career Fellowship and a Cure Cancer/Cancer Australia Priority-driven Collaborative Cancer Research grant (1163900) . J.A.M. is supported by a University of Melbourne Research Scholarship. K.D.S. and C.E.T. are supported by a Victorian Cancer Agency Mid-Career Research Fellowship (20026 and 18003) , and K.D.S. is supported by the Peter and Julie Alston Centenary Fellowship. C.L.G. is supported by funding from an NHMRC Early Career Fellowship (GNT1160963) . D.H.D.G is supported by Australian NHMRC Fellowships/grants (1090236, 1158024 and 1145888) , Cancer Council Victoria Grants-in-Aid (1146518 and 1102104) . M.L.A.L. is supported by funding from the Viertel Foundation Senior Medical Research Fellowship. This work is supported by an NHMRC Ideas Grant (GNT1182155) , The Harry Secomb Trust, the Jenny Tatchell Fund, and by funds from the Operational Infrastructure Support Program provided by the Victorian Government and NHMRC IRIISS (Independent Research Institutes Infrastructure Support Scheme) Grant. C.S. is a Royal Society Napier Research Professor (RSRP\R\210001) . His work is supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (CC2041) , the UK Medical Research Council (CC2041) , and the Wellcome Trust (CC2041) . C.S. is funded by Cancer Research UK (TRACERx (C11496/A17786) , PEACE (C416/A21999) and CRUK Cancer Immunotherapy Catalyst Network) ; Cancer Research UK Lung Cancer Centre of Excellence (C11496/A30025) ; the Rosetrees Trust, Butterfield and Stoneygate Trusts; Novo Nordisk Foundation (ID16584) ; Royal Society Professorship Enhancement Award (RP/EA/180007) ; National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre; the Cancer Research UK-University College London Centre; Experimental Cancer Medicine Centre; the Breast Cancer Research Foundation (US) (BCRF-22-157) ; Cancer Research UK Early Detection and Diagnosis Primer Award (grant EDDPMA-Nov21/100034) ; and The Mark Foundation for Cancer Research Aspire Award (grant 21-029-ASP) . This work was supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (grant number: SU2C-AACR-DT23-17 to S.M. Dubinett and A.E. Spira) . Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. C.S. is in receipt of an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 835297) .