Mucosal‐associated invariant T cells modulate innate immune cells and inhibit colon cancer growth
Olivia Cheng, Eric J. Lebish, Owen Jensen, Damian Jacenik, Shubhanshi Trivedi, Jackson G. Cacioppo, Jeffrey Aubé, Ellen J. Beswick, Daniel T. Leung
Abstract
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 showed that peritumoral injection of in vivo ‐ expanded MAIT cells into RAG1 −/− mice with MC38‐derived tumours inhibits tumour growth compared to control. Multiplex cytokine analyses showed that tumours from the MAIT cell‐treated group have higher expression of markers for eosinophil‐activating cytokines, suggesting a potential association between eosinophil recruitment and tumour inhibition. In a human peripheral leukocyte co‐culture model, we showed that leukocytes stimulated with MAIT ligand showed an increase in eotaxin‐1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we showed 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.