MAIT cells accumulate in ovarian cancer-elicited ascites where they retain their capacity to respond to MR1 ligands and cytokine cues

T Yao; PT Rudak; CM Laumont; AR Michaud; R Rashu; NN Knier; PJ Foster; HEG McWilliam; JA Villadangos; BH Nelson; GE DiMattia; TG Shepherd; SMM Haeryfar

Journal article

MAIT cells accumulate in ovarian cancer-elicited ascites where they retain their capacity to respond to MR1 ligands and cytokine cues

T Yao, PT Rudak, CM Laumont, AR Michaud, R Rashu, NN Knier, PJ Foster, HEG McWilliam, JA Villadangos, BH Nelson, GE DiMattia, TG Shepherd, SMM Haeryfar

Cancer Immunology Immunotherapy | Published : 2022

DOI: 10.1007/s00262-021-03118-9

Abstract

The low mutational burden of epithelial ovarian cancer (EOC) is an impediment to immunotherapies that rely on conventional MHC-restricted, neoantigen-reactive T lymphocytes. Mucosa-associated invariant T (MAIT) cells are MR1-restricted T cells with remarkable immunomodulatory properties. We sought to characterize intratumoral and ascitic MAIT cells in EOC. Single-cell RNA sequencing of six primary human tumor specimens demonstrated that MAIT cells were present at low frequencies within several tumors. When detectable, these cells highly expressed CD69 and VSIR, but otherwise exhibited a transcriptomic signature inconsistent with overt cellular activation and/or exhaustion. Unlike mainstream ..

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University of Melbourne Researchers

Hamish McWilliam Author

Jose Villadangos Author

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Grants

Awarded by Canadian Cardiovascular Society

Funding Acknowledgements

This work was funded by the Canadian Cancer Society (CCS) (Innovation Grant 706396 to S.M. Mansour Haeryfar) with support from the Spring Yard Cleanup for Cancer and also partially by a generous donor who wishes to remain anonymous. Celine M. Laumont is a recipient of a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (CIHR) (429161) and a Michael Smith Foundation for Health Research (MSFHR) fellowship (RT-2020-0630). Hamish E.G. McWilliam is supported by an Australian Research Council (ARC) Discovery Early Career Researcher Award (DE170100575) and the AMP's Tomorrow Fund. Jose A. Villadangos is supported by National Health and Medical Research Council (NHMRC) Research Fellowships (1117017 and 1058193) and Program Grant (1113293) and by an ARC Discovery Grant (170102471). Brad H. Nelson is supported by grants from CIHR (427647), Canada Foundation for Innovation (36239) and BC Cancer Foundation.