IFNG, a double-edged sword in cancer immunity and metastasis

IFNg has antitumorigenic effects; however, the findings of IFNg in promoting the tumor cell survival and inducing adaptive immune resistance via CD4 ^þ T-cell loss and programmed death ligand 1 (PD-L1) upregulation challenge this concept. Lo and colleagues determined that IFNg induces epithelial–mesenchymal transition (EMT) by regulating the turnover of miRNA in prostate cancer, emphasizing the duplicitous effects of IFNg. 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 IFNg–STAT1–IFIT5–miRNA–EMT pathway in prostate cancer progression. The biphasic effects of IFNg in prostate cancer raise concerns about its therapeutic application, which need to be evaluated in future studies.