Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy
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Ruan F.V. Medrano1,*, Aline Hunger1,*, Samir Andrade Mendonça1, José Alexandre M. Barbuto2,3 and Bryan E. Strauss1
1Viral 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
2Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
3Cell and Molecular Therapy Center, NUCEL-NETCEM, University of São Paulo, São Paulo, Brazil
*These authors contributed equally to this work
Keywords: IFNAR1/2, JAK-STAT, apoptosis, necroptosis, immunogenic cell death
Received: May 04, 2017 Accepted: July 12, 2017 Published: July 25, 2017
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.
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