Inhibition of yes-associated protein down-regulates PD-L1 (CD274) expression in human malignant pleural mesothelioma

Ping Chih Hsu, Jinbai Miao, Yu Cheng Wang, Wen Qian Zhang, Yi Lin Yang, Chih Wei Wang, Cheng Ta Yang, Zhen Huang, Joanna You, Zhidong Xu, David M. Jablons, Liang You*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

40 Scopus citations

Abstract

Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells. In H2052 and 211H cells, PD-L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD-L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD-L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD-L1 enhancer region encompassing 2 putative YAP-TEAD-binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD-L1 concurrently expressed in immunohistochemistry stain (n = 70, P <.05, chi-square). We conclude that PD-L1 is correlated with YAP expression, and inhibition of YAP down-regulates PD-L1 expression in human MPM. Further study of how YAP regulates PD-L1 in MPM is warranted.

Original languageEnglish
Pages (from-to)3139-3148
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number6
DOIs
StatePublished - 06 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Keywords

  • PD-L1
  • checkpoint immunotherapy
  • hippo signaling
  • malignant pleural mesothelioma
  • yes-associated protein

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