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

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

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i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
IMM - Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Departamento de Patologia e Oncologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.


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.


cancer microenvironment; immune contexture; immunoregulation; immunotherapy; type II interferon

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