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01-12-2021 | Cytokines | Original Article

Exhaustion in tumor-infiltrating Mucosal-Associated Invariant T (MAIT) cells from colon cancer patients

Authors: William Rodin, Patrik Sundström, Filip Ahlmanner, Louis Szeponik, Kamil Kajetan Zajt, Yvonne Wettergren, Elinor Bexe Lindskog, Marianne Quiding Järbrink

Published in: Cancer Immunology, Immunotherapy | Issue 12/2021

Abstract

Mucosal-associated invariant T (MAIT) cells are unconventional T cells recognizing microbial metabolites, presented by the invariant MR1 protein. Upon activation, MAIT cells rapidly secrete cytokines and exert cytotoxic functions, and may thus be highly relevant also in tumor immunity. MAIT cells accumulate in colon tumors, but in contrast to other cytotoxic T cell subsets, their presence in tumors has been associated with worse patient outcome. Here we investigated if exhaustion may contribute to reduced anti-tumor immunity by MAIT cells. Freshly isolated lymphocytes from colon tumors, unaffected tissue and blood from the same patients were analyzed by flow cytometry to detect MAIT cells with effector functions that are relevant for tumor immunity, and their expression of inhibitory receptors and other exhaustion markers. Our studies show that MAIT cells with a PD-1^highTim-3⁺CD39⁺ terminally exhausted phenotype and an increased proliferation accumulate in colon tumors. The exhausted MAIT cells have reduced polyfunctionality with regard to production of important anti-tumor effector molecules, and blocking antibodies to PD-1 partly improved activation of tumor-infiltrating MAIT cells in vitro. We conclude that the tumor microenvironment leads to exhaustion not only of conventional T cells, but also MAIT cells, and that checkpoint blockade therapy may be useful also to reinvigorate tumor-infiltrating MAIT cells.

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Title: Exhaustion in tumor-infiltrating Mucosal-Associated Invariant T (MAIT) cells from colon cancer patients
Authors: William Rodin
Patrik Sundström
Filip Ahlmanner
Louis Szeponik
Kamil Kajetan Zajt
Yvonne Wettergren
Elinor Bexe Lindskog
Marianne Quiding Järbrink
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keyword: Cytokines
Published in: Cancer Immunology, Immunotherapy / Issue 12/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02939-y

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