Type I Interferon in Chronic Virus Infection and Cancer

Laura M. Snell, Tracy L. McGaha, David G. Brooks

Research output: Contribution to journalReview articlepeer-review

261 Scopus citations


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. IFN-Is drive multiple feedforward and feedback mechanisms promoting inflammatory immunity in a regulated fashion. However, in response to chronic exposure, these regulatory mechanisms may predominate and suppress immunity, thereby promoting pathogen or tumor persistence. In viral infection, IFN-Is are induced, often at high levels, by multiple pattern or damage recognition receptors. In cancer, IFN-Is are likely induced by a more restricted set of receptors recognizing tumor cell death. The magnitude and mode of death may ultimately be determinant factors driving the development of functional inflammatory or regulatory immunity. IFN-I-induced negative regulatory pathways are emerging as key drivers of chronic inflammation in chronic virus infections and barriers to anticancer checkpoint-inhibitor therapy. However, the benefits and risks of therapeutically enhancing or nullifying IFN-Is and their downstream effectors must be carefully weighed, given the role of IFN-Is as both drivers and suppressors of immune responses.

Original languageEnglish (US)
Pages (from-to)542-557
Number of pages16
JournalTrends in Immunology
Issue number8
StatePublished - Aug 2017
Externally publishedYes


  • 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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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