Department of Cardiothoracic Surgery, Weill Cornell Medicine and NY Presbyterian Hospital, New York, New York.
Biochemistry, Cell & Molecular Biology Graduate Program, Weill Cornell Medicine, New York, New York.
Cancer Immunol Res. 2023 Jul 5;11(7):866-874. doi: 10.1158/2326-6066.CIR-22-0953.
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.
程序性死亡配体 1（PD-L1）是程序性死亡蛋白 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 免疫检查点轴已被成功靶向以增强抗肿瘤免疫反应。将 PD-L1 连接到膜上可空间限制其抑制免疫反应的能力，并通过调节其运输来提供 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 配体的功能，并且控制 PD-L1 在不同细胞内隔室中的驻留可能有助于调节这些活性。因此，控制 PD-L1 的运输正在成为其生物学的一个关键特征。在此，我们重点关注 PD-L1 运输的当前理解，并综述目前尝试在癌细胞中靶向该过程以增强抗肿瘤免疫的治疗方法。
