The role of transforming growth factor-β (TGF-β) in the formation of exhausted CD8 + T cells.

CD8 + T cells exert a critical role in eliminating cancers and chronic infections, and can provide long-term protective immunity. However, under the exposure of persistent antigen, CD8 + T cells can differentiate into terminally exhausted CD8 + T cells and lose the ability of immune surveillance and disease clearance. New insights into the molecular mechanisms of T-cell exhaustion suggest that it is a potential way to improve the efficacy of immunotherapy by restoring the function of exhausted CD8 + T cells. Transforming growth factor-β (TGF-β) is an important executor of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Recent studies have shown that TGF-β is one of the drivers for the development of exhausted CD8 + T cells. In this review, we summarized the role and mechanisms of TGF-β in the formation of exhausted CD8 + T cells and discussed ways to target those to ultimately enhance the efficacy of immunotherapy.