胃癌组织中PD-L1表达分析及两种功能性单克隆抗体阻断肿瘤相关PD-L1信号传导

J Sun, K Xu, C Wu, Y Wang, Y Hu, Y Zhu, Y Chen, Q Shi, G Yu, X Zhang
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引用次数: 70

摘要

程序性死亡-1配体-1 (Programmed death-1 ligand-1, PD-L1)是B7共刺激分子家族中的一员,在调节细胞和体液免疫应答中起重要作用。本研究成功制备了两种小鼠抗人PD-L1单克隆抗体10E10和2H11,并对其进行了进一步的表征。单克隆抗体10E10结合不同的PD-L1表位,比较了一系列恶性细胞系、活化的T淋巴细胞、B淋巴细胞和树突状细胞上可用的抗PD-L1单克隆抗体。然后用单克隆抗体2H11免疫组化染色,发现PD-L1在人胃癌标本中表达,而在正常组织和胃腺瘤组织中均未表达。另有数据显示,PD-L1是评价胃癌预后的决定性因素,抗人PD-L1单克隆抗体10E10可抑制肿瘤相关PD-L1诱导的t细胞凋亡。综上所述,我们制备的两种功能性小鼠抗人PD-L1单克隆抗体可能对进一步探索共刺激分子调控网络和肿瘤免疫治疗的免疫干预具有重要价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies.

Programmed death-1 ligand-1 (PD-L1), a member of the B7 family of costimulatory molecules, plays an important role in the regulations of the cellular and humoral immune responses. In this study, two mouse anti-human PD-L1 monoclonal antibodies named 10E10 and 2H11 were successfully generated and further characterized. Monoclonal antibody 10E10 bound to distinct PD-L1 epitope comparing an available anti-PD-L1 monoclonal antibody on a series of malignant cell lines, activated T lymphocytes, B lymphocytes and dendritic cells. Then, by using immunohistochemistry staining with monoclonal antibody 2H11, the expression of PD-L1 was found in human gastric carcinoma specimens but not in normal or gastric adenoma tissues. Additional data show that PD-L1 can be regarded as a decisive factor in evaluating gastric carcinoma prognosis and anti-human PD-L1 monoclonal antibody 10E10 could inhibit T-cell apoptosis induced by tumor-associated PD-L1. Taken together, these results showed that the two functional mouse anti-human PD-L1 monoclonal antibodies we generated might be of great value for further exploration of the costimulatory molecule regulating network and immunointervention for tumor immunotherapy.

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Tissue antigens
Tissue antigens 医学-病理学
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