Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
J Exp Clin Cancer Res. 2021 Jun 4;40(1):184. doi: 10.1186/s13046-021-01987-7.
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.
细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）/B7 和程序性死亡受体 1（PD-1）/程序性死亡配体 1（PD-L1）是两个最具代表性的免疫检查点途径，它们在 T 细胞激活的不同阶段负调控 T 细胞免疫功能。针对 CTLA-4/B7 和 PD1/PD-L1 途径的抑制剂彻底改变了多种癌症类型的免疫治疗。尽管联合抗 CTLA-4/B7 和抗 PD1/PD-L1 治疗显示出有希望的临床疗效，但只有一小部分接受抗 CTLA-4/B7 或抗 PD1/PD-L1 治疗的患者经历了延长的生存。PD-L1 和 CTLA-4 的表达调控对治疗效果有重大影响。深入了解 PD-L1 和 CTLA-4 的机制和相互作用可以帮助确定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，讨论了 PD-L1 和 CTLA-4 在 DNA、RNA 和蛋白质水平上的调控，以及生物标志物的间接调控、细胞内定位和药物。具体而言，已经开发出一些潜在的药物来高效调节 PD-L1 和 CTLA-4 的表达。
