Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.
Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.
复制标题
免疫检查点PD-L1和CTLA-4在癌症中的调节机制
DOI：
10.1186/s13046-021-01987-7
复制
发表时间：
2021-06-04
期刊：
影响因子：
--
通讯作者：
Cheng Q
中科院分区：
文献类型：
--
作者：
Zhang H;Dai Z;Wu W;Wang Z;Zhang N;Zhang L;Zeng WJ;Liu Z;Cheng Q
细胞毒性T淋巴细胞相关抗原4（CTLA-4）/B7和程序性死亡1（PD-1）/程序性细胞死亡配体1（PD-L1）是两条最具代表性的免疫检查点通路，它们在T细胞激活的不同阶段负向调节T细胞免疫功能。针对 CTLA-4/B7 和 PD1/PD-L1 通路的抑制剂彻底改变了多种癌症类型的免疫疗法。尽管抗CTLA-4/B7和抗PD1/PD-L1联合治疗已显示出良好的临床疗效，但只有一小部分接受抗CTLA-4/B7或抗PD1/PD-L1治疗的患者获得了延长的生存期。 PD-L1和CTLA-4表达的调节显着影响治疗效果。了解 PD-L1 和 CTLA-4 的深入机制和相互作用可以帮助识别具有更好免疫治疗反应的患者并促进他们的临床护理。在这篇综述中，我们在 DNA、RNA 和蛋白质水平上讨论了 PD-L1 和 CTLA-4 的调节，以及生物标志物、细胞内定位和药物的间接调节。具体来说，一些潜在的药物已经被开发出来，可以高效调节PD-L1和CTLA-4的表达。在线版本包含可在 10.1186/s13046-021-01987-7 获取的补充材料。
The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) are two most representative immune checkpoint pathways, which negatively regulate T cell immune function during different phases of T-cell activation. Inhibitors targeting CTLA-4/B7 and PD1/PD-L1 pathways have revolutionized immunotherapies for numerous cancer types. Although the combined anti-CTLA-4/B7 and anti-PD1/PD-L1 therapy has demonstrated promising clinical efficacy, only a small percentage of patients receiving anti-CTLA-4/B7 or anti-PD1/PD-L1 therapy experienced prolonged survival. Regulation of the expression of PD-L1 and CTLA-4 significantly impacts the treatment effect. Understanding the in-depth mechanisms and interplays of PD-L1 and CTLA-4 could help identify patients with better immunotherapy responses and promote their clinical care. In this review, regulation of PD-L1 and CTLA-4 is discussed at the levels of DNA, RNA, and proteins, as well as indirect regulation of biomarkers, localization within the cell, and drugs. Specifically, some potential drugs have been developed to regulate PD-L1 and CTLA-4 expressions with high efficiency. The online version contains supplementary material available at 10.1186/s13046-021-01987-7.
登录
查看更多内容
影响因子：
11.2
作者：
Barsoum, Ivraym B.;Smallwood, Chelsea A.;Graham, Charles H.
通讯作者：
Graham, Charles H.
PD-L1 通过 NF-kappa B 途径被 EBV 驱动的 LMP1 上调，并与自然杀伤/T 细胞淋巴瘤的不良预后相关
影响因子：
28.5
作者：
Bi XW;Wang H;Zhang WW;Wang JH;Liu WJ;Xia ZJ;Huang HQ;Jiang WQ;Zhang YJ;Wang L
通讯作者：
Wang L
影响因子：
--
作者：
Booth L;Roberts JL;Poklepovic A;Avogadri-Connors F;Cutler RE;Lalani AS;Dent P
通讯作者：
Dent P
影响因子：
--
作者：
Booth L;Roberts JL;Poklepovic A;Kirkwood J;Dent P
通讯作者：
Dent P
影响因子：
--
作者：
Carbotti G;Barisione G;Airoldi I;Mezzanzanica D;Bagnoli M;Ferrero S;Petretto A;Fabbi M;Ferrini S
通讯作者：
Ferrini S