Targeting immunosuppression by TGF-ß1 for cancer immunotherapy.

ABSTRACT

The TGF-ß1 cytokine is a key mediator of many biological processes. Complex regulatory mechanisms are in place that allow one single molecule to exert so many distinct indispensable activities. The complexity of TGF-ß1 biology is further illustrated by the opposing dual roles it plays during cancer progression. Risks of toxicities combined with lack of convincing therapeutical efficacy explain at least in part why therapies targeting TGF-ß1 have lagged behind in past decades. However, recent successes of immunostimulatory antibodies for the immunotherapy of cancer and findings that TGF-ß1 activity associates with resistance to immunotherapeutic drugs have revived the field. In this review, we discuss the biology of TGF-ß1 with a special focus on its roles in regulating immune responses in the context of cancer. We describe the various therapeutic approaches available to inhibit TGF-ß signalling, and more recent findings that allow selective targeting of specific sources of TGF-ß activity, which may prove relevant to increase the efficacy and reduce the toxicity of cancer immunotherapy.