Department of Urology, Comprehensive Cancer Center, University of California Davis, Sacramento, California.
Cancer Res. 2019 Mar 15;79(6):1032-1033. doi: 10.1158/0008-5472.CAN-19-0083.
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..
IFNγ 具有抗肿瘤作用;然而,IFNγ 通过 CD4 T 细胞缺失和程序性死亡配体 1(PD-L1)上调促进肿瘤细胞存活并诱导适应性免疫抵抗的发现,对这一概念提出了挑战。Lo 及其同事确定 IFNγ 通过调节前列腺癌中 miRNA 的周转来诱导上皮-间充质转化(EMT),强调了 IFNγ 的双重作用。IFIT5 是一种 IFN 诱导的四肽重复(IFIT)家族成员,被发现与外切核酸酶 XRN1 形成复合物,以加工 miRNA 成熟。这些发现揭示了前列腺癌进展中一种新的 IFNγ-STAT1-IFIT5-miRNA-EMT 通路。IFNγ 在前列腺癌中的双相作用引起了人们对其治疗应用的关注,这需要在未来的研究中进行评估。