Cancer cells employ programmed cell death ligand-1 (PD-L1), an immune checkpoint protein that binds to programmed cell death-1 (PD-1) and is highly expressed in various cancers, including cervical carcinoma, to abolish T-cell-mediated immunosurveillance. Despite a key role of PD-L1 in various cancer cell types, the regulatory mechanism for PD-L1 expression is largely unknown. Understanding this mechanism could provide a novel strategy for cervical cancer therapy. Here, we investigated the influence of ezrin/radixin/moesin (ERM) family scaffold proteins, crosslinking the actin cytoskeleton and certain plasma membrane proteins, on the expression of PD-L1 in HeLa cells. Our results showed that all proteins were expressed at mRNA and protein levels and that all ERM proteins were highly colocalized with PD-L1 in the plasma membrane. Interestingly, immunoprecipitation assay results demonstrated that PD-L1 interacted with ERM as well as actin cytoskeleton proteins. Furthermore, gene silencing of ezrin, but not radixin and moesin, remarkably decreased the protein expression of PD-L1 without affecting its mRNA expression. In conclusion, ezrin may function as a scaffold protein for PD-L1; regulate PD-L1 protein expression, possibly via post-translational modification in HeLa cells; and serve as a potential therapeutic target for cervical cancer, improving the current immune checkpoint blockade therapy.

中文翻译：

---

Ezrin 调节人宫颈腺癌细胞中程序性细胞死亡配体 1 的细胞表面表达

癌细胞利用程序性细胞死亡配体-1 (PD-L1) 来消除 T 细胞，这是一种与程序性细胞死亡-1 (PD-1) 结合的免疫检查点蛋白，在包括宫颈癌在内的多种癌症中高度表达。介导的免疫监视。尽管 PD-L1 在多种癌细胞类型中发挥着关键作用，但 PD-L1 表达的调节机制在很大程度上尚不清楚。了解这一机制可以为宫颈癌治疗提供新策略。在这里，我们研究了 ezrin/radixin/moesin (ERM) 家族支架蛋白（交联肌动蛋白细胞骨架和某些质膜蛋白）对 HeLa 细胞中 PD-L1 表达的影响。我们的结果表明，所有蛋白质均在 mRNA 和蛋白质水平上表达，并且所有 ERM 蛋白质与质膜中的 PD-L1 高度共定位。有趣的是，免疫沉淀测定结果表明 PD-L1 与 ERM 以及肌动蛋白细胞骨架蛋白相互作用。此外，ezrin 的基因沉默显着降低了 PD-L1 的蛋白表达，但不影响其 mRNA 表达，而 radixin 和 moesin 则没有。总之，ezrin 可能作为 PD-L1 的支架蛋白发挥作用；可能通过 HeLa 细胞中的翻译后修饰调节 PD-L1 蛋白表达；并作为宫颈癌的潜在治疗靶点，改善目前的免疫检查点阻断疗法。