Uncovering the Immunoregulatory Function and Therapeutic Potential of the PD-1/PD-L1 Axis in Cancer.
Uncovering the Immunoregulatory Function and Therapeutic Potential of the PD-1/PD-L1 Axis in Cancer.
复制标题
揭示PD-1/PD-L1轴在癌症中的免疫调节功能和治疗潜力。
DOI：
10.1158/0008-5472.can-21-2926
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发表时间：
2021-10-15
期刊：
影响因子：
11.2
通讯作者：
Zou W
中科院分区：
文献类型：
--
作者：
Pitter MR;Zou W
免疫检查点阻断涉及抗原呈递细胞和/或肿瘤细胞与效应T细胞之间的免疫抑制相互作用的靶向拮抗作用。阻断B7-H1（也称为程序性死亡配体1（PD-L1））可防止抑制性PD-L1分子与T细胞上的程序性细胞死亡受体1（PD-1）连接，从而增强肿瘤特异性T细胞对肿瘤细胞的反应。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增加了T细胞对肿瘤细胞的溶解，并表明肿瘤PD-L1形成了阻止肿瘤细胞溶解的“盾牌”。与其他原始的小鼠和人类研究一起，这项工作为新一代癌症治疗提供了科学依据，重点是靶向肿瘤微环境中的抑制性PD-1/PD-L1信号通路。
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.