Type I Interferon in Chronic Virus Infection and Cancer

Trends Immunol. 2017 Aug;38(8):542-557. doi: 10.1016/j.it.2017.05.005. Epub 2017 May 31.


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.

Keywords: CD4 T cell; CD8 T cell; HCV; HIV; LCMV; T cell exhaustion; cancer; chronic virus; dendritic cell; immune activation; immunotherapy; innate immunity; interferon alpha; interferon beta; macrophage; persistent virus; tumor; type I interferon.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antiviral Agents / therapeutic use
  • Chronic Disease
  • Humans
  • Immune Tolerance / immunology
  • Inflammation / etiology
  • Inflammation / immunology
  • Interferon Type I / immunology*
  • Interferon Type I / therapeutic use
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Virus Diseases / complications
  • Virus Diseases / drug therapy
  • Virus Diseases / immunology*


  • Antineoplastic Agents
  • Antiviral Agents
  • Interferon Type I