PD-1 and its ligands are important immune checkpoints in cancer.
PD-1 and its ligands are important immune checkpoints in cancer.
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DOI：
10.18632/oncotarget.13895
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发表时间：
2017-01-10
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
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作者：
Dong Y;Sun Q;Zhang X
检查点程序性死亡-1（PD-1）/程序性细胞死亡配体（PD-L）已被确定为促进肿瘤细胞免疫逃避的负性免疫调节分子。 PD-1 和 PD-L 的相互作用抑制 T 细胞和肿瘤浸润淋巴细胞 (TIL) 的功能，同时增强免疫抑制性调节性 T 细胞 (Treg) 的功能。这种情况导致肿瘤细胞逃避免疫反应。因此，PD-1/PD-L1的阻断通过减少Treg的数量和/或抑制活性以及通过恢复效应T细胞的活性来增强抗肿瘤免疫。此外，一些阻断PD-1/PD-Ls轴的单克隆抗体也取得了良好的效果，并获得了食品药品监督管理局的批准。 PD-1/PD-L 在肿瘤中的作用已得到充分研究，但人们对 PD-1 阻断 T 细胞激活的机制知之甚少。在本研究中，我们简要概述了肿瘤中PD-1和PD-L1失调的发现和调控机制，以及PD-1及其配体的功能和信号通路；还研究了它们在肿瘤逃避和临床治疗中的作用。
Checkpoint programmed death-1 (PD-1)/programmed cell death ligands (PD-Ls) have been identified as negative immunoregulatory molecules that promote immune evasion of tumor cells. The interaction of PD-1 and PD-Ls inhibits the function of T cells and tumor-infiltrating lymphocytes (TIL) while increasing the function of immunosuppressive regulatory T cells (Tregs). This condition causes the tumor cells to evade immune response. Thus, the blockade of PD-1/PD-L1 enhances anti-tumor immunity by reducing the number and/or the suppressive activity of Tregs and by restoring the activity of effector T cells. Furthermore, some monoclonal antibodies blockading PD-1/PD-Ls axis have achieved good effect and received Food and Drug Administration approval. The role of PD-1/PD-Ls in tumors has been well studied, but little is known on the mechanism by which PD-1 blocks T-cell activation. In this study, we provide a brief overview on the discovery and regulatory mechanism of PD-1 and PD-L1 dysregulation in tumors, as well as the function and signaling pathway of PD-1 and its ligands; their roles in tumor evasion and clinical treatment were also studied.