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Uncovering the Immunoregulatory Function and Therapeutic Potential of the PD-1/PD-L1 Axis in Cancer
Cancer Research ( IF 11.2 ) Pub Date : 2021-10-15 , DOI: 10.1158/0008-5472.can-21-2926
Michael R Pitter 1, 2, 3 , Weiping Zou 1, 2, 3
Affiliation  

Immune checkpoint blockade involves the targeted antagonism of immunosuppressive interactions between antigen-presenting cells and/or tumor cells and effector T cells. Blockade of B7-H1, also known as programmed death-ligand 1 (PD-L1), prevents the ligation of inhibitory PD-L1 molecules to programmed cell death receptor 1 (PD-1) on T cells, engendering a potentiated response of tumor-specific T cells against tumor cells. In a Cancer Research article, Hirano and colleagues showed that T-cell–mediated tumor immunity becomes impaired when tumor cells interact with T cells via PD-L1 in the mouse tumor microenvironment. They showed that targeting PD-L1 or PD-1 with mAbs increased tumor cell lysis by T cells and suggested that tumor PD-L1 forms a “shield” preventing tumor cell lysis. Alongside other original mouse and human studies, this work generated scientific rationales for a new generation of cancer treatment focused on targeting the inhibitory PD-1/PD-L1 signaling pathway in the tumor microenvironment. See related article by Hirano and colleagues, Cancer Res 2005;65: [1089–96][1] [1]: /lookup/volpage/65/1089?iss=3

中文翻译:

揭示癌症中 PD-1/PD-L1 轴的免疫调节功能和治疗潜力

免疫检查点阻断涉及靶向拮抗抗原呈递细胞和/或肿瘤细胞与效应T细胞之间的免疫抑制相互作用。阻断 B7-H1,也称为程序性死亡配体 1 (PD-L1),可阻止抑制性 PD-L1 分子与 T 细胞上的程序性细胞死亡受体 1 (PD-1) 连接,从而增强肿瘤的反应-针对肿瘤细胞的特异性 T 细胞。在一篇癌症研究文章中,Hirano 及其同事表明,当肿瘤细胞在小鼠肿瘤微环境中通过 PD-L1 与 T 细胞相互作用时,T 细胞介导的肿瘤免疫就会受损。他们表明,用 mAb 靶向 PD-L1 或 PD-1 会增加 T 细胞对肿瘤细胞的裂解,并表明肿瘤 PD-L1 形成了防止肿瘤细胞裂解的“屏障”。除了其他原始的小鼠和人类研究外,这项工作为新一代癌症治疗提供了科学依据,重点针对肿瘤微环境中的抑制性 PD-1/PD-L1 信号通路。参见 Hirano 及其同事的相关文章,Cancer Res 2005;65: [1089–96][1] [1]: /lookup/volpage/65/1089?iss=3
更新日期:2021-10-15
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