Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-alpha and IFN-beta, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-alpha/beta share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes. For example, type I IFNs drive not only the high maturation status of DCs, but also have a direct impact in cytotoxic T lymphocytes, NK cell activation, induction of tumor cell death and inhibition of angiogenesis. A variety of stimuli, including some standard cancer treatments, promote the expression of endogenous IFN-alpha/beta, which then participates as a fundamental component of immunogenic cell death. Systemic treatment with recombinant protein has been used for the treatment of melanoma. The induction of endogenous IFN-alpha/beta has been tested, including stimulation through pattern recognition receptors. Gene therapies involving IFN-alpha/beta have also been described. Thus, harnessing type I IFNs as an effective tool for cancer therapy continues to be studied.