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bioRxiv · 10.1101/2024.01.16.575894

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Cheng, O. J.·Lebish, E. J.·Jensen, O.·Jacenik, D.·Trivedi, S.·Cacioppo, J.·Aube, J.·Beswick, E. J.·Leung, D. T.
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Abstract

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 and have potentials for use as adoptive cell therapy. However, studies into their anti-cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we show that peritumoral injection of in vivo-expanded MAIT cells into RAG1-/- mice with MC38-derived tumors inhibits tumor growth compared to control. 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. In a human peripheral leukocyte co-culture model, we show that leukocytes stimulated with MAIT ligand show an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we show that MAIT cells have a protective role in a murine colon cancer model, associated with modulation of the immune response to cancer, potentially involving eosinophil-associated mechanisms. Our results highlight the potential of MAIT cells for non-donor restricted colon cancer immunotherapy. Brief summaryIn models of colon cancer, MAIT cells have anti-tumor activity, associated with increased production of proinflammatory and eosinophil-modulating cytokines.

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Cheng, O. J., Lebish, E. J., Jensen, O., Jacenik, D., Trivedi, S., Cacioppo, J., Aube, J., Beswick, E. J., Leung, D. T.. 2024-01-20. MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth. https://doi.org/10.1101/2024.01.16.575894

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