Regulation of PD-L1 Trafficking from Synthesis to Degradation.
Regulation of PD-L1 Trafficking from Synthesis to Degradation.
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DOI：
10.1158/2326-6066.cir-22-0953
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发表时间：
2023-07-05
影响因子：
10.1
通讯作者：
McGraw, Timothy E.
中科院分区：
文献类型：
--
作者：
Lemma, Eyoel Yemanaberhan;Letian, Anudari;Altorki, Nasser K.;McGraw, Timothy E.
程序性死亡配体1（PD-L1）是程序性细胞死亡蛋白1（PD-1）的跨膜配体，PD-1是一种抑制T细胞活性的受体。PD-L1/PD-1免疫检查点轴已成功靶向增强抗肿瘤免疫应答。将PD-L1束缚于膜在空间上限制了其抑制免疫应答的能力，并且通过调节其运输提供了对PD-L1质膜密度的急性和可逆调节。PD-L1具有独立于其作为PD-1配体的作用的功能，并且控制PD-L1在不同细胞内区室中的驻留可能有助于调节这些活性。因此，对PD-L1贩运的控制正在成为其生物学的一个关键特征。在此，我们专注于目前对PD-L1运输的低估，并回顾目前试图在癌细胞中治疗靶向这一过程以增强抗肿瘤免疫力的尝试。
Programmed death-ligand 1 (PD-L1) is a transmembrane ligand for the programmed cell death protein 1 (PD-1), a receptor that inhibits T-cell activity. The PD-L1/PD-1 immune checkpoint axis has been successfully targeted to enhance antitumor immune responses. Tethering PD-L1 to the membrane spatially restricts its ability to inhibit immune responses, and it provides for the acute and reversible modulation of PD-L1 plasma membrane density by regulation of its trafficking. PD-L1 has functions that are independent of its role as a ligand for PD-1, and control of PD-L1 residence in different intracellular compartments might contribute to the regulation of those activities. Thus, control of PD-L1 trafficking is emerging as a key feature of its biology. Herein, we focus on current understating of PD-L1 trafficking and review current attempts to therapeutically target this process in cancer cells to enhance antitumor immunity.