MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions. Despite their potential for adoptive cell therapy, studies into their anti-cancer activity, including their role in colon cancer, are limited. We expanded MAIT cells in vivo and injected them into RAG1 -/- mice with MC38-derived tumors and tumor growth was assessed. Peritumoral injection of MAIT cells inhibits tumor growth compared to control. Genomic and multiplex cytokine analyses show that tumors from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting an association between eosinophil recruitment and tumor inhibition. Multiplex cytokine and flow cytometry analyses of human peripheral leukocytes stimulated with MAIT ligand show an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. We documented that MAIT cells have a protective role in a murine colon cancer model, potentially involving novel eosinophil-associated mechanisms. This study provides evidence of the immune modulating potential of MAIT cells within the tumor microenvironment, leading to compositional and functional changes. Our results highlight the potential of MAIT cells for colon cancer immunotherapy.