The microbiota shapes the life trajectory of mucosal-associated invariant T cells

Mucosal-associated invariant T (MAIT) cells are innate-like T cells predominantly located in barrier tissues such as the lung, liver, skin, and colon. These cells recognize metabolites derived from the riboflavin biosynthetic pathway, which can rapidly traverse epithelial barriers and be presented during MAIT cell differentiation in the thymus and maturation in peripheral tissues. Furthermore, microbial metabolites significantly influence MAIT cell functions in various conditions, including cancer. This review summarizes how the microbiota shapes the life trajectory of MAIT cells and their antitumor reactivity. Additionally, we discuss the therapeutic implications of manipulating the microbiota as a 'bug-drug' strategy to enhance MAIT cell antitumor immunity, particularly in mucosal cancers, while emphasizing challenges and future directions for integrating microbiota considerations into MAIT cell-based therapies.