Regulation and Function of the PD-L1 Checkpoint.

Regulation and Function of the PD-L1 Checkpoint.
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DOI:
10.1016/j.immuni.2018.03.014
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发表时间:
2018-03-20
期刊:
影响因子:
32.4
通讯作者:
Schumacher TN
Schumacher TN
中科院分区:
医学1区
文献类型:
--
作者:
Sun C;Mezzadra R;Schumacher TN

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程序性死亡配体1(PD-L1)的表达经常在人类癌症中观察到。PD-L1与活化T细胞上的受体PD-1的结合通过抵消T细胞活化信号来抑制抗肿瘤免疫。基于抗体的PD-1-PD-L1抑制剂可以在患有多种晚期癌症的患者中诱导持久的肿瘤缓解,因此PD-L1在肿瘤细胞和肿瘤微环境中的其他细胞上的表达具有重要的临床意义。在这里,我们回顾了PD-1-PD-L1轴在癌症中的作用,重点是最近发现的机制,调节PD-L1在转录,转录后和蛋白质水平的表达。我们将这些知识放在临床观察的背景下,并讨论它如何为设计更精确和有效的癌症免疫检查点疗法提供信息。
Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level. We place this knowledge in the context of observations in the clinic and discuss how it may inform the design of more precise and effective cancer immune checkpoint therapies.
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