Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion

Front Immunol. 2018 May 4;9:847. doi: 10.3389/fimmu.2018.00847. eCollection 2018.


Interferon-gamma (IFN-γ) is a pleiotropic molecule with associated antiproliferative, pro-apoptotic and antitumor mechanisms. This effector cytokine, often considered as a major effector of immunity, has been used in the treatment of several diseases, despite its adverse effects. Although broad evidence implicating IFN-γ in tumor immune surveillance, IFN-γ-based therapies undergoing clinical trials have been of limited success. In fact, recent reports suggested that it may also play a protumorigenic role, namely, through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, and upregulation of indoleamine 2,3-dioxygenase and of checkpoint inhibitors, as programmed cell-death ligand 1. However, the IFN-γ-mediated responses are still positively associated with patient's survival in several cancers. Consequently, major research efforts are required to understand the immune contexture in which IFN-γ induces its intricate and highly regulated effects in the tumor microenvironment. This review discusses the current knowledge on the pro- and antitumorigenic effects of IFN-γ as part of the complex immune response to cancer, highlighting the relevance to identify IFN-γ responsive patients for the improvement of therapies that exploit associated signaling pathways.

Keywords: cancer microenvironment; immune contexture; immunoregulation; immunotherapy; type II interferon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytokines / immunology
  • Humans
  • Immune Evasion*
  • Immunologic Surveillance*
  • Immunotherapy
  • Interferon-gamma / immunology*
  • Interferon-gamma / therapeutic use
  • Mice
  • Neoplasms / immunology*
  • Signal Transduction
  • Tumor Microenvironment*


  • Cytokines
  • Interferon-gamma