Blockade of TGF-β signaling: a potential target for cancer immunotherapy?

Introduction: Malignant tumors often escape surveillance and eventual destruction by the host immune system through a variety of strategies including production of transforming growth factor (TGF)-β. Because of its generally immunosuppressive role, TGF-β has emerged as a promising therapeutic target in cancer immunotherapy. Areas covered: This article looks at specific mechanisms of how TGF-β controls the function of various immune cell subsets in the tumor microenvironment and focusses on T-cells. Various inhibition tools of TGF-β signaling and potential targets of therapeutic intervention are assessed along with the recent progress in combining TGF-β blockade and immune-mediated therapies. To round off the article, a summary of results from clinical trials is provided in which TGF-β blockade has shown therapeutic benefit for patients. Expert opinion: Data from preclinical models have shown that blocking TGF-β signaling can overcome resistance mechanisms and in combination with immune-checkpoint therapies, can yield additive or synergistic anti-tumor responses. The future of immunooncology will therefore be based on combination trials. Since response rates may critically depend on both cancer type and stage, selection of only those patients who can benefit from combinatorial immunotherapy regimens is of utmost importance.