Regulation and Functions of Protumoral Unconventional T Cells in Solid Tumors

Abstract

The vast majority of studies on T cell biology in tumor immunity have focused on peptide-reactive conventional T cells that are restricted to polymorphic major histocompatibility complex molecules. However, emerging evidence indicated that unconventional T cells, including γδ T cells, natural killer T (NKT) cells and mucosal-associated invariant T (MAIT) cells are also involved in tumor immunity. Unconventional T cells span the innate–adaptive continuum and possess the unique ability to rapidly react to nonpeptide antigens via their conserved T cell receptors (TCRs) and/or to activating cytokines to orchestrate many aspects of the immune response. Since unconventional T cell lineages comprise discrete functional subsets, they can mediate both anti- and protumoral activities. Here, we review the current understanding of the functions and regulatory mechanisms of protumoral unconventional T cell subsets in the tumor environment. We also discuss the therapeutic potential of these deleterious subsets in solid cancers and why further feasibility studies are warranted.

Thymus-derived hormonal and cellular control of cancer

“…These cells present highly diverse TCR, each composed of a heterodimeric αβ chain, to recognize processed antigenic peptide presented by MHC molecules on other cells ( Figure 1B ). Besides conventional T cells, other types of T lymphocytes also developed in the thymus, such as Treg and innate-like unconventional T cells (including MAIT, NKT and γδ T cells), orchestrate the immune responses against tumor cells ( 54 , 55 ), as summarized in Figure 2B and reviewed below.…”