Journal
NATURE CANCER
Volume 3, Issue 6, Pages 696-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s43018-022-00376-z
Keywords
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Categories
Funding
- Wellcome Trust [203141/Z/16/Z]
- Common Fund of the Office of the Director of the National Institutes of Health
- NCI
- NHGRI
- NHLBI
- NIDA
- NIMH
- NINDS
- Wellcome Trust Clinical Research Career Development Fellowship [220589/Z/20/Z]
- Academy of Medical Sciences Starter Grant for Clinical Lecturers
- National Institute for Health Research (NIHR) Academic Clinical Lectureship
- NIHR University College London Hospitals Biomedical Research Centre
- ideas 2 innovation translation scheme at the Francis Crick Institute
- Breast Cancer Research Foundation (BCRF)
- Cancer Research UK (CRUK) Early Detection and Diagnosis Project award
- CRUK
- NIHR
- Rosetrees Trust
- UKI NETs
- Francis Crick Institute from CRUK [FC001169]
- UK Medical Research Council [FC001169]
- CRUK Lung Cancer Centre of Excellence [C11496/A30025]
- Butterfield Trust
- Stoneygate Trust
- NovoNordisk Foundation [16584]
- Royal Society Professorship Enhancement Award [RP/EA/180007]
- NIHR Biomedical Research Centre at University College London Hospitals
- CRUK-University College London Centre
- Experimental Cancer Medicine Centre
- BCRF
- Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant [SU2C-AACR-DT23-17]
- European Research Council (ERC) under the European Union [FP7/2007-2013, FP7-THESEUS-617844]
- European Commission ITN [FP7-PloidyNet 607722]
- ERC Advanced Grant (PROTEUS) from the ERC under the European Union's Horizon 2020 research and innovation program [835297]
- Chromavision from the European Union's Horizon 2020 research and innovation program [665233]
- Wellcome Trust [220589/Z/20/Z] Funding Source: Wellcome Trust
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This study demonstrates the presence of resident V delta 1 gamma delta T cells in human lung tissues, particularly enriched in lung tumors with memory and effector phenotypes. The intratumoral V delta 1 T cells exhibit stem-like features and immune functions beneficial to the patient post-surgery. Integrating V delta 1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer is of great importance.
Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of V delta 1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission. Murine tissues harbor signature gamma delta T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident gamma delta cells are less well defined. In the present study, we show that human lung tissues harbor a resident V delta 1 gamma delta T cell population. Moreover, we demonstrate that V delta 1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral V delta 1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8(+) T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA(-)CD27(-) effector memory V delta 1 T cells in tumors and, most strikingly, with the numbers of CD103(+) tissue-resident V delta 1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating V delta 1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer.
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