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Scand J Immunol ; 100(3): e13391, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38773691

RESUMO

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.


Assuntos
Neoplasias do Colo , Eosinófilos , Imunidade Inata , Camundongos Knockout , Células T Invariantes Associadas à Mucosa , Animais , Células T Invariantes Associadas à Mucosa/imunologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/terapia , Camundongos , Humanos , Imunidade Inata/imunologia , Eosinófilos/imunologia , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Linhagem Celular Tumoral , Técnicas de Cocultura , Proteínas de Homeodomínio
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