The Two Faces of Interferon-γ in Cancer

Interferon-gamma 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-gamma 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-gamma 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-gamma/IFN-gamma receptor pathway may prove to be a viable new therapeutic target for a subset of malignancies. Clin Cancer Res; 17(19); 6118-24. (C) 2011 AACR.