TGF-beta: a master switch in tumor immunity

Abstract

The capacity of the immune system to distinguish foreign from self-antigen, and to subsequently eliminate the threat of disease without injuring the host is crucial for survival. It also serves to defend against tumor formation and progression via a process termed cancer immunosurveillance. Innate and adaptive immune cell types and effector molecules collectively function as extrinsic tumorsuppressor mechanisms. However, tumors may escape immunesurveillance through a variety of mechanisms that create a local microenvironment that is unfavorable for effective tumor immunity. Transforming growth factor β (TGF-β) has pleiotropic effects on the immune system, and is recognized as one of the most potent immunosuppressive agents in facilitating oncogenesis. The TGF-β pathway promotes cancer progression by concomitantly enhancing tumor metastases while inhibiting the protective host immunity. In this review, we discuss mechanisms through which TGF-β interferes with the development of an anti-tumor immunity and potential means through which to circumvent its activity in order to define more effective cancer immunotherapies.