Type I Interferon in Chronic Virus Infection and Cancer

• Published in: Trends in immunology Vol. 38; no. 8; pp. 542 - 557
• Main Authors: Snell, Laura M, McGaha, Tracy L, Brooks, David G
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2017; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Antineoplastic Agents - therapeutic use; Antiviral Agents - therapeutic use; Cancer; CD4 T cell; CD8 T cell; Chronic Disease; Chronic illnesses; Chronic infection; chronic virus; dendritic cell; Feedback; HCV; HIV; Human immunodeficiency virus; Humans; immune activation; Immune response; Immune system; Immune Tolerance - immunology; Immunosuppression; Immunotherapy; Inflammation; Inflammation - etiology; Inflammation - immunology; innate immunity; Interferon; interferon alpha; interferon beta; Interferon Type I - immunology; Interferon Type I - therapeutic use; Kinases; LCMV; macrophage; Neoplasms - complications; Neoplasms - drug therapy; Neoplasms - immunology; Ovarian cancer; persistent virus; Signal Transduction - drug effects; Signal Transduction - physiology; T cell exhaustion; tumor; type I interferon; Virus Diseases - complications; Virus Diseases - drug therapy; Virus Diseases - immunology; Viruses; Weapons; interferon beta; CD8 T cell; LCMV; immune activation; CD4 T cell; T cell exhaustion; macrophage; type I interferon; HIV; innate immunity; persistent virus; tumor; immunotherapy; HCV; cancer; interferon alpha; chronic virus; dendritic cell
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2017.05.005

Type I interferons (IFN-Is) are emerging as key drivers of inflammation and immunosuppression in chronic infection. Control of these infections requires IFN-I signaling; however, prolonged IFN-I signaling can lead to immune dysfunction. IFN-Is are also emerging as double-edged swords in cancer, providing necessary inflammatory signals, while initiating feedback suppression in both immune and cancer cells. Here, we review the proinflammatory and suppressive mechanisms potentiated by IFN-Is during chronic virus infections and discuss the similar, newly emerging dichotomy in cancer. We then discuss how this understanding is leading to new therapeutic concepts and immunotherapy combinations. We propose that, by modulating the immune response at its foundation, it may be possible to widely reshape immunity to control these chronic diseases.