PD-1/PD-L1调控及其在肿瘤靶向治疗的前景展望

doi:10.24920/21804

摘要/Abstract

摘要：

PD-1/PD-L1 是重要的免疫检查点,PD-1/PD-L1功能障碍导致肿瘤转移和免疫逃逸。PI3K/Akt/mTOR、MAPK 信号网络诱导PD-1/PD-L1表达并促进肿瘤发展;转录因子 HIF、PTEN、p53、CDK5、BRD4、STAT 调节PD-1/PD-L1表达;PD-1/PD-L1水平也受表观修饰和翻译后修饰调节,以上调控机制均作为潜在的肿瘤治疗靶点。目前,PD-1/PD-L1单克隆抗体及小分子抑制剂联合治疗肿瘤在临床上取得了良好的效果。

关键词: PD-1/PD-L1, 免疫治疗, 调控机制, 临床试验, 抑制剂

Abstract:

Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) is a significant immune checkpoint, and the dysfunction of this axis contributes to tumor metastasis and immune escape. PI3K/Akt/mTOR and MAPK signal network induces PD-1/PD-L1 expression and facilitates tumor progression. Transcriptional factors such as hypoxia induced factors, PTEN, p53, CDK5, BRD4, STAT modulate PD-1/PD-L1 expression. PD-1/PD-L1 level is also regulated via epigenetic and post-translational manner. The underlying mechanisms mentioned above may provide potential targets for tumor treatment. At present, the combination therapy of PD-1/PD-L1 monoclonal antibodies plus small molecular inhibitors has achieved good outcomes in tumor treatment.

Key words: programmed cell death protein 1/programmed death ligand 1, immunotherapy, regulation, clinical trial, inhibitors

Ni Jieming, Ni Anping. Landscape of PD-1/PD-L1 Regulation and Targeted Immunotherapy[J].Chinese Medical Sciences Journal, 2018, 33(3): 174-182.

图/表 1

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