The Role of Yes-Associated Protein (YAP) in Regulating Programmed Death-Ligand 1 (PD-L1) in Thoracic Cancer

• Main Authors: Ping-Chih Hsu, Cheng-Ta Yang, David M. Jablons, Liang You
• Format: Article
• Language: English
• Published: MDPI AG 2018-12-01
• Series: Biomedicines
• Subjects: yes-associated protein (YAP); programmed death-ligand 1 (PD-L1); non-small cell lung cancer (NSCLC); malignant pleural mesothelioma (MPM); immunotherapy
• Online Access: https://www.mdpi.com/2227-9059/6/4/114

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.