MAIT Cells: Partners or Enemies in Cancer Immunotherapy?

SIMPLE SUMMARY: Unconventional T cells have recently come under intense scrutiny because of their innate-like effector functions and unique antigen specificity, suggesting their potential importance in antitumor immunity. MAIT cells, one such population of unconventional T cell, have been shown to significantly influence bacterial infections, parasitic and fungal infections, viral infections, autoimmune and other inflammatory diseases, and, as discussed thoroughly in this review, various cancers. This review aims to merge accumulating evidence, tease apart the complexities of MAIT cell biology in different malignancies, and discuss how these may impact clinical outcomes. While it is clear that MAIT cells can impact the tumor microenvironment, the nature of these interactions varies depending on the type of cancer, subset of MAIT cell, patient demographic, microbiome composition, and the type of therapy administered. This review examines the impact of these variables on MAIT cells and discusses outstanding questions within the field. ABSTRACT: 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.