Mucosal‐associated invariant T cells modulate innate immune cells and inhibit colon cancer growth

Author:

Cheng Olivia J.12ORCID,Lebish Eric J.3ORCID,Jensen Owen12ORCID,Jacenik Damian34ORCID,Trivedi Shubhanshi2ORCID,Cacioppo Jackson G.5ORCID,Aubé Jeffrey5ORCID,Beswick Ellen J.36ORCID,Leung Daniel T.12ORCID

Affiliation:

1. Division of Microbiology & Immunology, Department of Pathology University of Utah Salt Lake City Utah USA

2. Division of Infectious Disease, Department of Internal Medicine University of Utah Salt Lake City Utah USA

3. Division of Gastroenterology, Department of Internal Medicine University of Utah Salt Lake City Utah USA

4. Department of Cytobiochemistry, Faculty of Biology and Environmental Protection University of Lodz Lodz Poland

5. Department of Chemistry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

6. Division of Digestive Diseases and Nutrition, Department of Internal Medicine University of Kentucky Lexington Kentucky USA

Abstract

AbstractMucosal‐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 vivoexpanded 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.

Funder

National Institutes of Health

Publisher

Wiley

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