MAIT Cells Come to the Rescue in Cancer Immunotherapy?

Abstract

Recent progress in immunobiology has led to the observation that, among cells classically categorized as the typical representatives of the adaptive immune system, i.e., T cells, some possess the phenotype of innate cells. Invariant T cells are characterized by T cell receptors recognizing a limited range of non-peptide antigens, presented only in the context of particular molecules. Mucosal-associated invariant T cells (MAIT cells) are an example of such unconventional cells. In humans, they constitute between 1% and 8% of the peripheral blood T lymphocytes and are further enriched in mucosal tissues, mesenteric lymph nodes, and liver, where they can account for even 40% of all the T cells. MAIT cells recognize antigens in the context of major histocompatibility complex class I-related protein (MR1). Upon activation, they instantly release pro-inflammatory cytokines and mediate cytolytic function towards bacterially infected cells. As such, they have been a rapidly evolving research topic not only in the field of infectious diseases but also in the context of many chronic inflammatory diseases and, more recently, in immuno-oncology. Novel findings suggest that MAIT cells function could also be modulated by endogenous ligands and drugs, making them an attractive target for therapeutic approaches. In this review, we summarize the current understanding of MAIT cell biology, their role in health and disease and discuss their future potential in cancer immunotherapy. This is discussed through the prism of knowledge and experiences with invariant natural killer T cells (iNKT)—another prominent unconventional T cell subset that shares many features with MAIT cells.

Reconstitution of T Cell Subsets Following Allogeneic Hematopoietic Cell Transplantation

“…Mucosal-associated invariant T (MAIT) cells comprise 1-10% of CD3 + cells and are abundant in both PB and mucosal tissues. They are innate-like T cells that highly express CD161 and a semi-invariant αβ TCRs that recognize microbial metabolites presented by MR1 [89]. MAIT cells can be activated in MR1-dependent and MR1-independent ways, although expansion requires circulating B cells and commensal microbiota [89][90][91][92].…”

“…They are innate-like T cells that highly express CD161 and a semi-invariant αβ TCRs that recognize microbial metabolites presented by MR1 [89]. MAIT cells can be activated in MR1-dependent and MR1-independent ways, although expansion requires circulating B cells and commensal microbiota [89][90][91][92]. In the allo-HCT setting, no associations between high MAIT cell numbers and protection from infections have been reported so far [93].…”

“…No associations with incorporation of TBI [93], glucocorticoids and calcineurin inhibitors [92] with MAIT cell recovery were found. However, immunosuppressive therapy-induced proinflammatory signals [89,91], along with an altered gut microbiota composition as a result of conditioning therapy, as well as altered dietary intake and antibiotic use [99], might further influence MAIT cell reconstitution and function after allo-HCT.…”

“…Invariant NKT (iNKT) cells are rare innate-like T cells with immunomodulatory functions, which express semi-invariant αβ TCRs that recognize lipid antigens presented by CD1d molecules. Similar to MAIT cells, they are capable of secreting large amounts of cytokines upon activation in TCR-dependent and TCR-independent manners [89]. High numbers of iNKT cells in the graft and early after allo-HCT are associated with protection against GvHD [101][102][103][104][105][106] and relapse [103,106,107] and seems to be correlated with improved overall survival [103].…”

Chronic Viral Liver Diseases: Approaching the Liver Using T Cell Receptor-Mediated Gene Technologies

“…As summarized in Table 2, various subsets of unconventional T cells can be enriched at rather high numbers, and they have garnered much interest in cancer immunotherapy [118,119]. Among the three major subtypes, MAIT cells, and γδT cells represent the major T cell populations in the liver, with some studies showing that each of those subsets can comprise up to around half of all T lymphocytes in healthy human liver [103,120,121].…”