MR1-Restricted T Cells Are Unprecedented Cancer Fighters

Front Immunol. 2020 Apr 28:11:751. doi: 10.3389/fimmu.2020.00751. eCollection 2020.

Abstract

Non-polymorphic MHC class I-related molecule MR1 presents antigenic bacterial metabolites to mucosal-associated invariant T (MAIT) cells and self-antigens to MR1-restricted T (MR1T) cells. Both MR1-restricted T cell populations are readily identified in healthy individuals, with MAIT cells accounting for 1-10% of circulating T cells, while MR1T cells have frequencies comparable to peptide-specific T cells (<0.1%). Self-reactive MR1T cells display a heterogeneous phenotype, and are capable of releasing both TH1 and TH2 cytokines, supporting not only activation of inflammation but also contributing to its regulation. Importantly, MR1T cells recognize and kill a diverse range of MR1-expressing tumor cells. On the other hand, evidence suggests MAIT cells augment cancer growth and metastases. This review addresses the potential role of MR1-restricted T cells in controlling tumor cells, facilitating their elimination and regulating cancer immunity. We also discuss therapeutic opportunities surrounding MR1-restricted T cells in cancer.

Keywords: MR1; MR1T; T-cell therapy; self-antigens; tumor recognition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Cross Reactions
  • Cytokines / metabolism
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Mice
  • Minor Histocompatibility Antigens / metabolism*
  • Mucosal-Associated Invariant T Cells / immunology*
  • Neoplasms / immunology*
  • Phenotype
  • Receptors, Antigen, T-Cell / immunology

Substances

  • Autoantigens
  • Cytokines
  • Histocompatibility Antigens Class I
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • Mr1 protein, mouse
  • Receptors, Antigen, T-Cell