Tumor-infiltrating mucosal-associated invariant T (MAIT) cells retain expression of cytotoxic effector molecules
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Patrik Sundström1, Louis Szeponik1, Filip Ahlmanner1, Malin Sundquist1, Justin S.B. Wong2, Elinor Bexe Lindskog3, Bengt Gustafsson3 and Marianne Quiding-Järbrink1
1 Department of Microbiology and Immunology, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden
2 Department of Pathology, National University Hospital, Singapore and Department of Microbiology, National, University of Singapore, Singapore
3 Department of Surgery, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden
Keywords: tumor immunity; MAIT cells; cytotoxicity; colon adenocarcinoma; granzyme B
Received: November 15, 2018 Accepted: April 03, 2019 Published: April 19, 2019
Mucosal-associated invariant T (MAIT) cells all express a semi-invariable T cell receptor recognizing microbial metabolites presented on the MHC class I-like molecule MR1. Upon activation, they rapidly secrete cytokines and increase their cytotoxic potential. We showed recently that MAIT cells with Th1 phenotype accumulate in human colon adenocarcinomas. Here, we investigated the cytotoxic potential of tumor-infiltrating MAIT cells in colon adenocarcinomas, and to what extent it may be affected by the tumor microenvironment. Activation of MAIT cells from tumors induced increased Granzyme B, and to a lesser extent, perforin expression. Degranulation was assessed by surface expression of CD107a, and was also seen in response to cognate antigen recognition. The cytotoxic potential of tumor-associated MAIT cells was very similar to that of MAIT cells from unaffected colon. MAIT cells were also identified by immunofluorescence in direct contact with tumor cells in sections from colon cancer specimens. To summarize, tumor-associated MAIT cells from colon tumors have strong cytotoxic potential and are not compromised in this regard compared to MAIT cells from the unaffected colon. We conclude that MAIT cells may contribute significantly to the protective immune response to tumors, both by secretion of Th1- associated cytokines and by direct killing of tumor cells.
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