Curio, S. et al. (2022) NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression. Discovery Immunology, 1(1), kyac002. (doi: 10.1093/discim/kyac002) (PMID:36277678) (PMCID:PMC9580227)
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Abstract
γδT cells are unconventional T cells particularly abundant in mucosal tissues that play an important role in tissue surveillance, homeostasis and cancer. γδT cells recognize stressed cells or cancer cells through the NKG2D receptor to kill these cells and maintain normality. Contrary to the well-established anti-tumor function of these NKG2D-expressing γδT cells, we show here that, in mice, NKG2D regulates a population of pro-tumor γδT cells capable of producing IL-17A. Germline deletion of Klrk1, the gene encoding NKG2D, reduced the frequency of γδT cells in the tumor microenvironment and delayed tumor progression. We further show that blocking NKG2D reduced the capability of γδT cells to produce IL-17A in the pre-metastatic lung and that co-culture of lung T cells with NKG2D ligand-expressing tumor cells specifically increased the frequency of γδT cells. Together, these data support the hypothesis that in a tumor microenvironment where NKG2D ligands are constitutively expressed, γδT cells accumulate in an NKG2D-dependent manner and drive tumor progression by secreting pro-inflammatory cytokines, such as IL-17A.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the Wellcome Trust RCDF (RCDF088381/Z/09/Z to N.G.), a Wellcome Trust PhD studentship (203948/Z/16A to S.C.), the Stevenson Fund to S.C., Breast Cancer Now (2018JulPR1101 to S.B.C.), Cancer Research UK Glasgow Centre (A25142 to S.B.C.), Wellcome Trust (208990/Z/17/Z to S.B.C.), Marie Curie European Fellowship (GDCOLCA 800112 to T.S.) and Naito Foundation Grant for Research Abroad (to T.S). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Wiesheu, Robert and Coffelt, Dr Seth and Glauner, Teresa and Edwards, Dr Sarah and Kilbey, Dr Anna |
| Authors: | Curio, S., Edwards, S. C., Suzuki, T., McGovern, J., Triulzi, C., Yoshida, N., Jonsson, G., Glauner, T., Rami, D., Wiesheu, R., Kilbey, A., Purcell, R. V., Coffelt, S. B., and Guerra, N. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Discovery Immunology |
| Publisher: | Oxford University Press |
| ISSN: | 2754-2483 |
| ISSN (Online): | 2754-2483 |
| Published Online: | 10 May 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Discovery Immunology 1(1): kyac002 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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