Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 133, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.111057
Keywords
Oral cancer; Patient-derived tumor xenograft (PDTX) model; Triptolide; Programmed death ligand 1 (PD-L1); Interferon-gamma (IFN-gamma)
Funding
- Medical Affairs Bureau, Ministry of National Defense, Taiwan, Republic of China [MAB-106-090]
- Tri-Service General Hospital, Taiwan, Republic of China [TSGH-C105-006-008-S05, TSGH-C106-004-006-008-S05, TSGH-C107-008-S06, TSGH-C108-007-008-S06, TSGH-C108-179]
- Ministry of Science and Technology, Taiwan, Republic of China [MOST 105-2314-B-016-021-MY3]
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The study found significant overexpression of PD-L1 in oral squamous cell carcinoma tissues, and that IFN-gamma can drive PD-L1 expression in OSCC cells. Triptolide (TPL) can suppress oral cancer growth and downregulate PD-L1 expression in oral cancer cells in vitro.
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-gamma) 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-gamma on OSCC cell proliferation using enzyme-linked immunosorbent assays and found that IFN-gamma 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-gamma-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.
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