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Biomedicines. 2018 Dec 7;6(4). pii: E114. doi: 10.3390/biomedicines6040114.

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

Author information

1
Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA. 8902049@gmail.com.
2
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. 8902049@gmail.com.
3
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. yang1946@adm.cgmh.org.tw.
4
Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA. david.jablons@ucsfmedctr.org.
5
Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA. Liang.You@ucsf.edu.

Abstract

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.

KEYWORDS:

immunotherapy; malignant pleural mesothelioma (MPM); non-small cell lung cancer (NSCLC); programmed death-ligand 1 (PD-L1); yes-associated protein (YAP)

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