Immunotherapeutic Potential of TGF-β Inhibition and Oncolytic Viruses

In cancer immunotherapy, a patient’s own immune system is harnessed against cancer. Immune checkpoint inhibitors release the brakes on tumor-reactive T cells and, therefore, are particularly effective in treating certain immune-infiltrated solid tumors. By contrast, solid tumors with immune-silent profiles show limited efficacy of checkpoint blockers due to several barriers. Recent discoveries highlight transforming growth factor-β (TGF-β)-induced immune exclusion and a lack of immunogenicity as examples of these barriers. In this review, we summarize preclinical and clinical evidence that illustrates how the inhibition of TGF-β signaling and the use of oncolytic viruses (OVs) can increase the efficacy of immunotherapy, and discuss the promise and challenges of combining these approaches with immune checkpoint blockade. Immune checkpoint blockade is not effective in immune-excluded and -desert tumors due to an immunosuppressive tumor microenvironment and the absence of activated T cells.TGF-β is a pleiotropic cytokine that contributes to immune exclusion and evasion in various cancer types.The therapeutic efficacy of oncolytic viruses is built on the recruitment of T cells and the induction of tumor-reactive immunity.Oncolytic virotherapy and inhibition of TGF-β signaling, either alone or in combination, are two emerging approaches to increase the susceptibility of immune-silent tumors to immune checkpoint therapy.