Ni Jie-Ming, Ni An-Ping
Seven Year Program of China Medical University, Shenyang 110122, China.
Department of Clinical Laboratories, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Chin Med Sci J. 2018 Sep 20;33(3):174-182. doi: 10.24920/21804.
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.
程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）是一个重要的免疫检查点，该信号轴功能失调会导致肿瘤转移和免疫逃逸。PI3K/Akt/mTOR和MAPK信号网络诱导PD-1/PD-L1表达并促进肿瘤进展。缺氧诱导因子、PTEN、p53、CDK5、BRD4、STAT等转录因子调节PD-1/PD-L1表达。PD-1/PD-L1水平也通过表观遗传和翻译后方式进行调控。上述潜在机制可能为肿瘤治疗提供潜在靶点。目前，PD-1/PD-L1单克隆抗体联合小分子抑制剂的联合疗法在肿瘤治疗中取得了良好疗效。
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