PD-1 and its ligands are important immune checkpoints in cancer

被引:254
作者
Dong, Yinan [1 ]
Sun, Qian [1 ]
Zhang, Xinwei [1 ]
机构
[1] Tianjin Med Univ, Natl Clin Res Ctr Canc, Canc Inst & Hosp, Cell Immunol Lab,Tianjin Key Lab Canc Prevent & t, Tianjin, Peoples R China
基金
美国国家科学基金会;
关键词
PD-1; PD-L1; PD-L2; T cell anergy; immune checkpoint blockade; CELL LUNG-CANCER; CD8(+) T-CELLS; PROGRAMMED DEATH 1; ADVANCED MELANOMA; UP-REGULATION; TUMOR MICROENVIRONMENT; NEGATIVE REGULATION; PD-1/PD-L1; PATHWAY; ANTI-PD-1; ANTIBODY; EPITHELIAL-CELLS;
D O I
10.18632/oncotarget.13895
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2171 / 2186
页数:16
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