韩明媛 王振波

[摘要] Hippo-YAP/TAZ 通路在调节细胞增殖、存活和信号转导等生物学功能方面发挥着重要作用。近年来，该通路在肿瘤免疫调节中的作用被广泛研究，其不仅可以调节肿瘤微环境中的免疫细胞，还能在 mRNA 和蛋白水平上调控程序性死亡配体-1（PD-L1）的转录和翻译过程，进而影响程序性死亡受体-1（PD -1）/PD-L1免疫检查点抑制剂的疗效。此外，该通路还是肿瘤细胞耐药与免疫逃逸之间联系的桥梁。因此，全面了解 Hippo-YAP/TAZ 通路在免疫调节中的作用机制，可为临床抗肿瘤治疗寻求新的靶点，使更多患者在免疫治疗中获益。

[关键词] Hippo-YAP/TAZ 通路;肿瘤免疫调节; PD-1/PD-L1;免疫逃逸;作用机制

[中图分类号] R730.1 [文献标识码] A  [文章编号]2095-0616（2021）22-0049-04

Advances in the study of the role of Hippo-YAP/TAZ pathway in tumor immunity regulation

HAN  Mingyuan   WANG  Zhenbo

Department of Oncology， Affiliated Hospital of Binzhou Medical University， Shandong， Binzhou 256600， China  [Abstract] Hippo-YAP/TAZ pathway plays an important role in regulating biological functions such as cell proliferation， survival and signal transduction. In recent years， the role of this pathway in tumor immunity regulation has been extensively studied. A variety of studies showed that it not only regulates immune cells in the tumor microenvironment， but also regulates the transcription and translation processes of programmed death-ligand 1（PD-L1） at the messenger ribonucleic acid （mRNA） and protein levels， which further affects the efficacy of programmed cell death-1（PD-1）/PD-L1 immune checkpoint inhibitors. In addition， this pathway bridges the link between drug resistance and immune escape in tumor cells. Therefore， a comprehensive understanding of the mechanism of Hippo-YAP/TAZ pathway in immunity regulation can lead to new targets for antitumor therapy in clinic and enable more patients to benefit from immunotherapy.

[Key words] Hippo-YAP/TAZ pathway; Tumor immunity regulation; Programmed cell death-1/programmed death- ligand 1; Immune escape; Mechanism

近年来，肿瘤免疫检查点抑制剂（immune checkpoint  inhibitors，ICIs）成为临床关注的热点，其中，程序性死亡受体-1（programmed death protein 1，PD-1）/程序性死亡配体-1（programmed death ligand 1， PD-L1）抑制剂在临床治疗中应用较为广泛。免疫治疗的目的是启动免疫的自我循环过程，即癌症-免疫周期[1]，该循环中的任何一个环节都会影响免疫治疗的效果，接受免疫治疗的患者必须具有一定程度的免疫功能;同时，ICIs 的应用会导致某些免疫相关不良事件的发生[2]。因此，免疫耐药以及寻求更多、更精确的生物标志物成为临床治疗中亟待解决的问题[3]。

Hippo-YAP/TAZ 通路是一个高度保守的信号转导通路， Yes 相关蛋白（yes-associated protein， YAP）是该通路的转录共激活因子，在正常机体内， YAP 以磷酸化的形式参与信号转导的调节。当 Hippo 通路发生异常或 YAP 过表达时会破坏细胞的增殖-凋亡平衡，从而促进肿瘤的发生[4]。研究发现，该通路在免疫调节过程中发挥着重要作用[5]。……