Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma
Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2005.07.013
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发表时间：
2006-03-01
期刊：
影响因子：
4.8
通讯作者：
Azuma, M
中科院分区：
文献类型：
--
作者：
Tsushima, F;Tanaka, K;Azuma, M
我们检测了人口腔鳞状细胞癌 (SCC) 系中五种 B7 共刺激分子（B7-H1、B7-DC、B7h、CD80 和 CD86）的细胞表面表达。大多数人 SCC 细胞系表达不同水平的 B7-H1 和 B7-DC。它们的表达通过干扰素（IFN）-γ刺激进一步上调。免疫组织化学染色显示 B7-H1 在人原发性口腔 SCC 上大量且占主导地位的表达。小鼠SCC系NR-S1既不表达B7-H1也不表达B7-DC，但通过培养中的IFN-γ刺激和体内接种诱导B7-H1。尽管 NR-S1 肿瘤在免疫功能正常的同系小鼠中逐渐生长，但阻断性抗 β7-H1 或抗 PD-1 mAb 的给药显着抑制肿瘤生长，表明 PD-1:B7-H1 途径对宿主免疫反应的负调节。我们的结果表明，B7-H1 主要在 B7 家族分子内的口腔 SCC 上诱导。通过阻断 PD-1:B7-H1 通路成功抑制肿瘤生长可能意味着口腔鳞状细胞癌免疫治疗的新方法。 (c) 2005 Elsevier Ltd. 保留所有权利。
We examined cell surface expression of five B7 costimulatory molecules (B7-H1, B7-DC, B7h, CD80 and CD86) in human oral squamous cell carcinoma (SCC) lines. Most human SCC cell lines expressed various levels of B7-H1 and B7-DC. Their expression was further upregulated by interferon (IFN)-gamma stimulation. Immunohistochemical staining revealed substantial and predominant expression of B7-H1 on human primary oral SCC. A murine SCC line, NR-S1, neither expressed B7-H1 nor B7-DC, but induced B7-H1 by IFN-gamma stimulation in culture and the inoculation in vivo. Although NR-S1 tumors grew progressively in immunocompetent syngeneic mice, the administration of blocking anti-beta 7-Hl or anti-PD-1 mAb significantly inhibited the tumor growth, suggesting the negative regulation of host immune responses by the PD-1:B7-H1 pathway. Our results demonstrate that B7-H1 is predominantly induced on oral SCC within the B7 family molecules. A successful inhibition of tumor growth by blockade of the PD-1:B7-H1 pathway may implicate a new approach for immunotherapy of oral SCC. (c) 2005 Elsevier Ltd. All rights reserved.