雷公藤红素在干扰素 γ 调节的微环境中体外、体内及临床患者中抑制口腔癌细胞 PD-L1 的表达。
Triptolide suppresses oral cancer cell PD-L1 expression in the interferon-γ-modulated microenvironment in vitro, in vivo, and in clinical patients.
机构信息
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan; School of Dentistry, National Defense Medical Center, Taipei, Taiwan.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; School of Dentistry, National Defense Medical Center, Taipei, Taiwan.
出版信息
Biomed Pharmacother. 2021 Jan;133:111057. doi: 10.1016/j.biopha.2020.111057. Epub 2020 Dec 4.
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.
程序性死亡配体 1（PD-L1）在口腔鳞状细胞癌（OSCC）中的生物学和预后作用仍不清楚。此外，肿瘤微环境干扰素-γ（IFN-γ）在宿主对恶性细胞的反应、口腔癌生长和 PD-L1 表达中的关键作用尚未得到充分研究。因此，使用免疫组织化学分析了 130 例 OSCC 样本中的 PD-L1 表达，结果发现肿瘤部位的 PD-L1 表达显著上调（P<0.01）。我们进一步分析了 IFN-γ对 OSCC 细胞增殖的影响，发现 IFN-γ以剂量依赖的方式驱动 OSCC 细胞中 PD-L1 的表达。雷公藤红素（TPL）是从雷公藤中分离得到的一种具有生物活性的化合物，具有抗炎和抗肿瘤作用。为了研究 TPL 的抗肿瘤作用是否涉及 PD-L1 表达的抑制，我们用 TPL 体外处理 OSCC 细胞和患者来源的肿瘤异种移植（PDTX）模型。TPL 抑制 PDTX 模型中的 PD-L1 表达，抑制肿瘤生长，并在 IFN-γ 调节的微环境中抑制 OSCC 细胞中的 PD-L1 表达。我们得出结论，TPL 抑制口腔癌的肿瘤生长，并下调体外口腔癌细胞中的 PD-L1 表达。我们的研究结果为 OSCC 的 PD-L1 靶向治疗的临床开发提供了证据。
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