IFNγ, a Double-Edged Sword in Cancer Immunity and Metastasis.

Abstract

IFNγ has antitumorigenic effects; however, the findings of IFNγ in promoting the tumor cell survival and inducing adaptive immune resistance via CD4⁺ T-cell loss and programmed death ligand 1 (PD-L1) upregulation challenge this concept. Lo and colleagues determined that IFNγ induces epithelial-mesenchymal transition (EMT) by regulating the turnover of miRNA in prostate cancer, emphasizing the duplicitous effects of IFNγ. IFIT5, an IFN-induced tetratricopeptide repeat (IFIT) family member, was found to form a complex with the exoribonuclease-XRN1 to process miRNA maturation. These findings unveil a new IFNγ-STAT1-IFIT5-miRNA-EMT pathway in prostate cancer progression. The biphasic effects of IFNγ in prostate cancer raise concerns about its therapeutic application, which need to be evaluated in future studies.<i>See related article by Lo et al., p. 1098</i>.