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。
