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A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer.

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posted on 2022-06-30, 13:49 authored by Yin Wu, Dhruva Biswas, Ieva Usaite, Mihaela Angelova, Stefan Boeing, Takahiro Karasaki, Selvaraju Veeriah, Justyna Czyzewska-Khan, Cienne Morton, Magdalene Joseph, Sonya Hessey, James Reading, Andrew Georgiou, Maise Al Bakir, TRACERx Consortium, Nicholas McGranahan, Mariam Jamal-Hanjani, Allan Hackshaw, Sergio A Quezada, Adrian C Hayday, Charles Swanton
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.

Funding

Crick (Grant ID: 10093, Grant title: Hayday FC001093) Crick (Grant ID: 10169, Grant title: Swanton FC001169) European Research Council (Grant ID: 617844 - THESEUS, Grant title: ERC 617844 - THESEUS) European Research Council (Grant ID: 835297 - PROTEUS, Grant title: ERC 835297 - PROTEUS) Medical Research Council (Grant ID: MC_PC_17179, Grant title: CiC 2017: Crick Idea to Innovation (i2i)) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Novo Nordisk UK Research Foundation (Grant ID: NNF15OC0016584, Grant title: NovoNordisk Foundation 16584)

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