期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 40, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13046-021-01987-7
关键词
PD-L1; CTLA-4; Cancer immunotherapy; Regulatory mechanism; Drug intervention
类别
资金
- National Natural Science Foundation of China [82073893, 81873635, 81472693, 81903663]
- China Postdoctoral Science Foundation [2018M633002]
- Hunan Provincial Natural Science Foundation of China [2018SK2101, 2018JJ3838]
- Hunan Provincial Health Committee Foundation of China [C2019186]
- Xiangya Hospital Central South University postdoctoral foundation
The regulatory mechanisms of PD-L1 and CTLA-4 play a crucial role in immunotherapy, and understanding their interactions can help improve patients' treatment responses and clinical care.
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.
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