The two faces of interferon-γ in cancer

Clin Cancer Res. 2011 Oct 1;17(19):6118-24. doi: 10.1158/1078-0432.CCR-11-0482. Epub 2011 Jun 24.


Interferon-γ is a cytokine whose biological activity is conventionally associated with cytostatic/cytotoxic and antitumor mechanisms during cell-mediated adaptive immune response. It has been used clinically to treat a variety of malignancies, albeit with mixed results and side effects that can be severe. Despite ample evidence implicating a role for IFN-γ in tumor immune surveillance, a steady flow of reports has suggested that it may also have protumorigenic effects under certain circumstances. We propose that, in fact, IFN-γ treatment is a double-edged sword whose anti- and protumorigenic activities are dependent on the cellular, microenvironmental, and/or molecular context. As such, inhibition of the IFN-γ/IFN-γ receptor pathway may prove to be a viable new therapeutic target for a subset of malignancies.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Humans
  • Interferon-gamma / adverse effects
  • Interferon-gamma / physiology*
  • Interferon-gamma / therapeutic use
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Receptors, Interferon / physiology
  • Signal Transduction
  • Translational Medical Research


  • Receptors, Interferon
  • interferon gamma receptor
  • Interferon-gamma