Hsu Ping-Chih, Yang Cheng-Ta, Jablons David M, You Liang
Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
Biomedicines. 2018 Dec 7;6(4):114. doi: 10.3390/biomedicines6040114.
The programmed death-ligand 1(PD-L1)/PD-1 pathway is an immunological checkpoint in cancer cells. The binding of PD-L1 and PD-1 promotes T-cell tolerance and helps tumor cells escape from host immunity. Immunotherapy targeting the PD-L1/PD-1 axis has been developed as an anti-cancer therapy and used in treating advanced human non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Yes-associated protein (YAP) is a key mediator of the Hippo/YAP signaling pathway, and plays important roles in promoting cancer development, drug resistance and metastasis in human NSCLC and MPM. YAP has been suggested as a new therapeutic target in NSCLC and MPM. The role of YAP in regulating tumor immunity such as PD-L1 expression has just begun to be explored, and the correlation between YAP-induced tumorigenesis and host anti-tumor immune responses is not well known. Here, we review recent studies investigating the correlation between YAP and PD-L1 and demonstrating the mechanism by which YAP regulates PD-L1 expression in human NSCLC and MPM. Future work should focus on the interactions between Hippo/YAP signaling pathways and the immune checkpoint PD-L1/PD-1 pathway. The development of new synergistic drugs for immune checkpoint PD-L1/PD-1 blockade in NSCLC and MPM is warranted.
程序性死亡配体1(PD-L1)/程序性死亡受体1(PD-1)通路是癌细胞中的一个免疫检查点。PD-L1与PD-1的结合可促进T细胞耐受,并帮助肿瘤细胞逃避免疫监视。针对PD-L1/PD-1轴的免疫疗法已被开发为一种抗癌疗法,并用于治疗晚期人类非小细胞肺癌(NSCLC)和恶性胸膜间皮瘤(MPM)。Yes相关蛋白(YAP)是Hippo/YAP信号通路的关键介质,在促进人类NSCLC和MPM的癌症发展、耐药性和转移中发挥重要作用。YAP已被认为是NSCLC和MPM中的一个新的治疗靶点。YAP在调节肿瘤免疫(如PD-L1表达)中的作用刚刚开始被探索,YAP诱导的肿瘤发生与宿主抗肿瘤免疫反应之间的相关性尚不清楚。在此,我们综述了最近关于YAP与PD-L1相关性的研究,并阐述了YAP在人类NSCLC和MPM中调节PD-L1表达的机制。未来的工作应聚焦于Hippo/YAP信号通路与免疫检查点PD-L1/PD-1通路之间的相互作用。开发用于NSCLC和MPM中免疫检查点PD-L1/PD-1阻断的新型协同药物是很有必要的。