A recent boom in mucosal-associated invariant T (MAIT) cell research has identified relationships between MAIT cell abundance, function, and clinical outcomes in various malignancies. As they express a variety of immune checkpoint receptors and ligands, and possess strong cytotoxic functions, MAIT cells are an attractive new subject in the field of tumor immunology. MAIT cells are a class of innate-like T cells that express a semi-invariant T cell antigen receptor (TCR) that recognizes microbially derived non-peptide antigens presented by the non-polymorphic MHC class-1 like molecule, MR1. In this review, we outline the current (and often contradictory) evidence exploring MAIT cell biology and how MAIT cells impact clinical outcomes in different human cancers, as well as what role they may have in cancer immunotherapy.

While much of the research concerning factors associated with responses to immunotherapies focuses on the contributions of conventional peptide-specific T cells, the role of unconventional T cells, such as mucosalassociated invariant T (MAIT) cells, in human melanoma remains largely unknown. MAIT cells are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting vitamin metabolites derived from bacteria. In this prospective clinical study, we sought to characterize MAIT cells in melanoma patients and determine their association with clinical outcomes. We identified tumor-infiltrating MAIT cells in melanomas across metastatic sites and found that the number of circulating MAIT cells is reduced in melanoma patients. However, circulating MAIT cell frequency is restored by anti-PD1 treatment in responding patients, correlating with treatment responses in which patients with high frequencies of MAIT cells exhibited improved overall survival. These data provide evidence for leveraging MAIT cells and their functions as novel targets for future therapies.