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

Our plain-English summary of The Role of Yes-Associated Protein (YAP) in Regulating Programmed Death-Ligand 1 (PD-L1) in Thoracic Cancer, by P.C. Hsu, C.T. Yang, D.M. Jablons, et al (Biomedicines, 2018).

The study

• Authors: P.C. Hsu, C.T. Yang, D.M. Jablons, L. You
• Journal: Biomedicines
• Published: 2018;6(4)
• Type of article: Review
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This article was a review, not a new study. The authors summarized recent research on how yes-associated protein (YAP), a protein in the Hippo signaling pathway, relates to programmed death-ligand 1 (PD-L1), a molecule that helps tumor cells escape the immune system. They covered non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Much of the review described two earlier studies by the authors' own group. In human NSCLC and MPM tumor samples, positive YAP staining in the cell nucleus was significantly associated with positive PD-L1 expression. The review did not give the number of samples. In laboratory cell lines, lowering YAP reduced PD-L1, and adding extra YAP raised PD-L1 in two cell lines that started with low levels. A further test linked YAP to a DNA region that controls the PD-L1 gene. The authors concluded that YAP partly regulates the PD-L1/PD-1 immune checkpoint pathway in these cancers. They noted that most of this work had been done in cell lines, with only a few patient samples. The article did not discuss asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: review (narrative review of published studies, including two earlier studies by the same research group)
• Who was studied: Published research on human non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM), mainly the authors' two prior studies using human tumor samples and cell lines (H460, SKLU-1, H1299, H2052, 211H, A549, H2452). The review gives no patient numbers.
• Main results:
  • In the authors' earlier studies of human NSCLC and MPM tumor samples, positive nuclear YAP staining was significantly associated with positive PD-L1 expression (number of samples not given in this review)
  • In NSCLC and MPM cell lines (H460, SKLU-1, H1299, H2052 and 211H), knocking down YAP decreased PD-L1 protein and mRNA levels
  • Forced overexpression of YAP increased PD-L1 protein in A549 (NSCLC) and H2452 (MPM) cells, which have low YAP and PD-L1 expression
  • Chromatin immunoprecipitation using a YAP antibody pulled down the PD-L1 enhancer region containing two putative TEAD binding sites in NSCLC and MPM cell lines; the authors took this to indicate that YAP regulates PD-L1 transcription
• The authors' conclusion: The authors concluded that YAP plays a role in partially regulating the PD-L1/PD-1 immune checkpoint pathway in human NSCLC and MPM. They also concluded that future work should develop drugs targeting YAP to work alongside PD-L1/PD-1 blockade.
• Limitations the authors state:
  • Research on the link between YAP and PD-L1/PD-1 had mostly been done in cell lines, with only a few cohort patient samples
  • An ideal small animal model for studying interactions between human tumors and the immune system was lacking

Topics

Medical terms in this study, explained in our Lexicon: PD-L1, Immunotherapy, Non-Small Cell Lung Cancer, Pleural Mesothelioma, Metastasis, Carcinogenesis.

Related studies

• Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors — S.A. Kareff, S. Samtani, et al. (2021)
• Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) — S. Cedrés, S. Ponce-Aix, et al. (2015)
• Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: regulation and counterregulation — A.J. Currie, A. Prosser, et al. (2009)
• Analysis of expression of PTEN/PI3K pathway and programmed cell death ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) — S. Cedrés, S. Ponce-Aix, et al. (2016)
• The Predictive and Prognostic Nature of Programmed Death-Ligand 1 in Malignant Pleural Mesothelioma: A Systematic Literature Review — A.S. Mansfield, R.J. Brown, et al. (2022)
• Prognosis of patients with malignant mesothelioma by expression of programmed cell death 1 ligand 1 and mesothelin in a contemporary cohort in Finland — D. Vizcaya, B. Farahmand, et al. (2020)

Browse more research in Biomedicines, or return to medical research.