Posttranslational Modifications of PD-L1 and Their Applications in Cancer Therapy.
Posttranslational Modifications of PD-L1 and Their Applications in Cancer Therapy.
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DOI：
10.1158/0008-5472.can-18-1892
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发表时间：
2018-11-15
期刊：
影响因子：
11.2
通讯作者：
Hung MC
中科院分区：
文献类型：
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作者：
Hsu JM;Li CW;Lai YJ;Hung MC
PD-L1的翻译后修饰（PTMs）已成为调节癌症患者免疫抑制的重要调节机制。在暴露于炎症细胞因子时，癌细胞和抗原呈递细胞，如巨噬细胞和树突状细胞表达PD-L1，通过PD-1参与抑制效应T细胞的活性。近年来的研究表明，糖基化、磷酸化、泛素化、泛素化和乙酰化在PD-L1蛋白稳定性、易位和蛋白-蛋白相互作用的调控中发挥重要作用。ptm的异常改变直接影响pd - l1介导的免疫抵抗。在新发现的PD-L1 PTMs调控信号通路的基础上，研究人员通过靶向PD-L1 PTMs，研究了天然食品化合物、小分子抑制剂和单克隆抗体的癌症治疗潜力。这些临床前研究结果表明，靶向PD-L1的ptm产生了有希望的抗肿瘤效果，这些治疗策略的临床翻译是必要的。
Posttranslational modifications (PTMs) of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in cancer patients. In exposure to inflammatory cytokines, cancer cells and antigen-presenting cells, such as macrophages and dendritic cells express PD-L1 to inhibit the activity of effector T cells through PD-1 engagement. Recent studies suggested that glycosylation, phosphorylation, ubiquitination, sumoylation, and acetylation play important roles in the regulation of PD-L1 protein stability and translocation and protein-protein interactions. Aberrant alterations of PTMs directly influence PD-L1–mediated immune resistance. On the basis of the newly identified regulatory signaling pathways of PD-L1 PTMs, researchers have investigated the cancer therapeutic potential of natural food compounds, small-molecule inhibitors, and monoclonal antibodies by targeting PD-L1 PTMs. Results of these preclinical studies demonstrated that targeting PTMs of PD-L1 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted.