MAIT cells in gastrointestinal cancer: immunity to therapy.

Mucosal-associated invariant T (MAIT) cells are emerging as important regulators of immunity in gastrointestinal (GI) cancers. Enriched in mucosal and hepatic tissues, MAIT cells recognize microbial-derived metabolites presented by MHC class I-related molecule (MR1) and rapidly exert effector functions, including cytokine production and cytotoxicity. Across GI malignancies, including hepatocellular carcinoma, cholangiocarcinoma, colorectal, gastric, pancreatic, and esophageal cancers, MAIT cells display context-dependent roles shaped by the tumor microenvironment, microbiome, and immune signaling pathways. While they can mediate antitumor immunity, they frequently exhibit functional exhaustion or adopt pro-tumorigenic phenotypes. Therapeutic strategies aim to enhance MAIT cell activity, reverse dysfunction, and integrate them into combinatorial immunotherapy approaches. Understanding MAIT cell biology may enable their exploitation as biomarkers and therapeutic targets in GI cancers.