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Triptolide suppresses oral cancer cell PD-L1 expression in the interferon-γ-modulated microenvironment in vitro, in vivo, and in clinical patients.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Jan; Vol. 133, pp. 111057. Date of Electronic Publication: 2020 Dec 04. - Publication Year :
- 2021
-
Abstract
- Biological and prognostic roles of programmed death ligand 1 (PD-L1) remain unclear in oral squamous cell carcinoma (OSCC). Moreover, the pivotal role of tumor microenvironmental interferon-gamma (IFN-γ) in host responses to malignant cells, oral cancer growth, and PD-L1 expression has not been adequately studied. Thus, PD-L1 expression in 130 OSCC samples was analyzed using immunohistochemistry, which was found significantly overexpressed at the tumor site (P < .01). We further analyzed the effects of IFN-γ on OSCC cell proliferation using enzyme-linked immunosorbent assays and found that IFN-γ drives PD-L1 expression in OSCC cells in a dose-dependent manner. Triptolide (TPL), a bioactive compound isolated from Tripterygium wilfordii, exhibits anti-inflammatory and antitumor activities. To investigate whether the antitumor effect of TPL involves the suppression of PD-L1 expression, we treated OSCC cells in vitro and a patient-derived tumor xenograft (PDTX) model with TPL. TPL suppressed PD-L1 expression in the PDTX model, inhibiting tumor growth, and in OSCC cells in an IFN-γ-modulated microenvironment. We concluded that TPL inhibits tumor growth in oral cancer and downregulates PD-L1 expression in oral cancer cells in vitro. Our results provide evidence for the clinical development of PD-L1-targeted therapy for OSCC.<br /> (Copyright © 2020 National Defense Medical Center, Taiwan. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Animals
B7-H1 Antigen genetics
Cell Line, Tumor
Down-Regulation
Epoxy Compounds pharmacology
Female
Humans
Janus Kinase 2 metabolism
Male
Mice, Inbred NOD
Mice, SCID
Middle Aged
Mouth Neoplasms immunology
Mouth Neoplasms metabolism
Mouth Neoplasms pathology
STAT1 Transcription Factor metabolism
Signal Transduction
Squamous Cell Carcinoma of Head and Neck immunology
Squamous Cell Carcinoma of Head and Neck metabolism
Squamous Cell Carcinoma of Head and Neck pathology
Tumor Burden
Xenograft Model Antitumor Assays
Mice
B7-H1 Antigen metabolism
Cell Proliferation drug effects
Diterpenes pharmacology
Immune Checkpoint Inhibitors pharmacology
Interferon-gamma pharmacology
Mouth Neoplasms drug therapy
Phenanthrenes pharmacology
Squamous Cell Carcinoma of Head and Neck drug therapy
Tumor Microenvironment
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 133
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 33378962
- Full Text :
- https://doi.org/10.1016/j.biopha.2020.111057