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

The two faces of interferon-γ in cancer.

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Laboratory of Cancer Biology & Genetics, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, Maryland 20892, USA.


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.

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