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

Author(s)

Medrano, Ruan F. V. ; Hunger, Aline ; Mendonca, Samir Andrade ; Barbuto, Jose Alexandre M. ; Strauss, Bryan E.

• Document type: Review article
• Source: ONCOTARGET; v. 8, n. 41, p. 71249-71284, SEP 19 2017.
• Web of Science Citations: 25

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-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. (AU)

• FAPESP's process: 11/10656-5 - Evaluation of the molecular mechanisms of p53/ARF and IFN-beta pathways involved in the the response of melanoma cells to treatment with the p19Arf and IFN-beta transgenes.
• Grantee: Aline Hunger Ribeiro
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/26580-9 - Cancer gene therapy: strategic positioning for translational studies
• Grantee: Bryan Eric Strauss
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/09474-5 - Association of the immunotherapy mediated by p19Arf and Interferon-beta gene transfer with immunogenic cell death induced by the chemotherapic doxorubicin for the treatment of cancer
• Grantee: Ruan Felipe Vieira Medrano
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/25167-5 - P19Arf and interferon-beta gene transfer: delineating the importance of their combination in mouse models of cancer gene therapy
• Grantee: Bryan Eric Strauss
• Support Opportunities: Regular Research Grants