Effects of TGF-beta on the immune system: implications for cancer immunotherapy

Transforming growth factor-beta (TGF-beta) is a potent regulator of numerou s processes including hematopoiesis, cell proliferation, differentiation an d activation. TGF-beta has pleiotropic and profound effects on the immune s ystem and on hematologic malignancies, ie leukemia. It is the most potent i mmunosuppressor described to date. Evidence exists that the immunosuppressi ve potential of TGF-beta is an important promoter of malignant cell growth. This is partly caused by TGF-beta-induced interference with the generation of tumor-specific cytotoxic T lymphocytes, but also by TGF-beta-induced pr omotion of angiogenesis and tumor stroma formation. Until now, significant clinical responses have not been achieved with the current cancer immunothe rapeutic approaches. One of the possible explanations for this failure is i mmunosuppression induced by tumor-derived TGF-beta. Here, several strategie s to counteract the immunosuppressive effects of TGF-beta and the current l imitations of these strategies will be discussed. Knowledge of the mechanis ms by which TGF-beta interferes with the development of an anti-tumor respo nse and of the strategies to counteract these immunosuppressive activities is crucial to improve the current cancer immunotherapeutic approaches.