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Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 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 Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103+ tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer.

Original publication

DOI

10.1038/s43018-022-00376-z

Type

Journal article

Journal

Nature cancer

Publication Date

06/2022

Volume

3

Pages

696 - 709

Addresses

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. yin.wu@kcl.ac.uk.

Keywords

TRACERx Consortium, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Animals, Humans, Mice, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Receptors, Antigen, T-Cell, gamma-delta