Dual Roles of MAIT Cells in the Tumor Microenvironment: Implications for Cancer Immunity and Therapy

Mucosal-associated invariant T (MAIT) cells are innate T cells that recognize riboflavin metabolites with canonical TCRs and develop in the thymus as memory cells. They account for 1%-10% of peripheral blood T cells in humans and are frequently observed within the tumor microenvironment (TME). However, their functional roles remain controversial. In certain tumors, infiltrated MAIT cells upregulate cytotoxic receptor NKG2D and effector cytokines, including IFNγ, TNFα, and granzyme, contributing to tumor control. In other settings, they exhibit reduced cytokine production, increased expression of inhibitory receptors such as PD-1, CTLA-4, and TIM-3, and are associated with unfavorable clinical outcomes. These discrepancies are influenced by the source of MR1 ligands, cytokine composition, and metabolic conditions within the TME. Meanwhile, due to the innate cytotoxicity and lack of alloreactivity, MAIT cells are attractive candidates for cellular immunotherapy. This review summarizes the functional dichotomy of MAIT cells in cancers and outlines strategies to harness their anti-tumor properties.