Uncovering the mechanisms that regulate tumor-induced T-cell anergy

Abstract

Helper T cells become hyporesponsive in the tumor microenvironment (at least in part) owing to the NFAT1-dependent expression of anergy-associated genes. Anergy constitutes a crucial mechanism to prevent tumor destruction by T cells, and hence may represent a powerful target to boost antitumor immune responses and improve the efficacy of immunotherapy.

Keywords: NFAT; T helper cell; anergy; immune evasion; melanoma.

Figure 1. Tumor-induced helper T-cell anergy. The immunosuppressive tumor microenvironment induces anergy in helper T cells through the NFAT-dependent expression of anergy-inducing genes, coding for proteins that can inhibit TCR signaling and silence cytokine expression. The activation of this program can be caused by interferences with dendritic cell (DC) maturation, which might result in defective co-stimulation, although a direct role for other cells in the tumor microenvironment cannot be excluded. Anergic CD4⁺ T cells cannot efficiently “help” CD8⁺ T-cell antitumor responses, allowing cancer cells to escape CD8⁺ T cell-mediated lytic responses.