Triptolide suppresses oral cancer cell PD-L1 expression in the interferon-γ-modulated microenvironment in vitro, in vivo, and in clinical patients - 19/12/20
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Graphical abstract |
Highlights |
• | PD-L1 is overexpressed in oral cancer patients. |
• | TPL inhibits tumor growth in oral cancer models by downregulating PD-L1. |
• | IFN-γ increases cell proliferation and upregulates PD-L1 expression. |
• | TPL reduces IFN-γ secretion and inhibits the IFN-γ-related JAK2-STAT1 pathway. |
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.
El texto completo de este artículo está disponible en PDF.Keywords : Oral cancer, Patient-derived tumor xenograft (PDTX) model, Triptolide, Programmed death ligand 1 (PD-L1), Interferon-gamma (IFN-γ)
Esquema
Vol 133
Artículo 111057- janvier 2021 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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