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

// Ruan F.V. Medrano 1, * , Aline Hunger 1, * , Samir Andrade Mendonça 1 , José Alexandre M. Barbuto 2, 3 and Bryan E. Strauss 1 1 Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of São Paulo/LIM 24, University of São Paulo School of Medicine, São Paulo, Brazil 2 Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil 3 Cell and Molecular Therapy Center, NUCEL-NETCEM, University of São Paulo, São Paulo, Brazil * These authors contributed equally to this work Correspondence to: Bryan E. Strauss, email: bstrauss@usp.br , bryan.strauss@hc.fm.usp.br Keywords: IFNAR1/2, JAK-STAT, apoptosis, necroptosis, immunogenic cell death Received: May 04, 2017 Accepted: July 12, 2017 Published: July 25, 2017 ABSTRACT 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-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β 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-α/β, 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-α/β has been tested, including stimulation through pattern recognition receptors. Gene therapies involving IFN-α/β have also been described. Thus, harnessing type I IFNs as an effective tool for cancer therapy continues to be studied.