参与调控细胞程序性死亡蛋白1及其配体1信号通路的研究进展

Advances in research of regulation of PD-1/PD-L1 signaling pathway

细胞程序性死亡蛋白1及其配体1(PD-1/PD-L1)通路已经成为研究热点,无论在抗肿瘤还是在抗炎方面均取得了一定的成果,但具体的机制目前尚不完全清楚。本文介绍了PD-1及PD-L1的分子结构、功能以及与其他通路之间的关系。PD-1蛋白是免疫抑制分子,与其配体PD-L1结合起促进细胞凋亡的作用。在肿瘤或炎症中,JAK/STAT、NF-κB、MAPK、PI3K以及TIM-3/Gal-9等其他信号通路被激活,诱导免疫细胞及肿瘤细胞高表达PD-1及PD-L1,使免疫细胞活性降低,消耗增加,募集减少,从而使机体抗肿瘤、抗炎能力下降。PD-1/PD-L1与JAK/STAT、NF-κB、MAPK、PI3K以及TIM-3/Gal-9等其他信号通路也起相互调控作用。PD-1/PD-L1抑制剂与JAK/STAT、NF-κB、MAPK、PI3K以及TIM-3/Gal-9等通路抑制剂联合应用,在抗肿瘤以及肿瘤耐药性方面取得了突破性进展。然而,相对于PD-1/PD-L1对肿瘤作用的研究而言,PD-1/PD-L1在炎症方面的研究相对较少,无相应的药物应用于临床,需要大量的基础研究支持。

The programmed cell death protein 1(PD-1)and programmed death receptor ligand-1(PD-L1)pathway has become a hot research topic,and some results have been achieved both in anti-tumor and anti-inflammatory research.However,the specific mechanism is not completely clear.This article describes the molecular structure and function of PD-1 and PD-L1 and the relationship between PD-1 and PD-L1.PD-1 is an immunosuppressive molecule that binds to its ligand PD-L1 to promote apoptosis.In tumors or inflammation,other signaling pathways such as JAK/STAT,NF-κB,MAPK,PI3 K,and TIM-3/Gal-9 are activated,inducing immune cells and tumor cells to overexpress PD-1 and PD-L1.As a result,immune cell activity is reduced,consumption is increased,and recruitment is reduced,which reduces the body’s ability to resist tumors and inflammation.PD-1/PD-L1 interacts with other signaling pathways such as JAK/STAT,NF-κB,MAPK,PI3 K,and TIM-3/Gal-9,and PD-1/PD-L1 inhibitors can be used in combination with JAK/STAT,NF-κB,MAPK,PI3 K,and TIM-3/Gal-9 pathway inhibitors;much progress has been achieved in anti-tumor therapy and tumor drug resistance.However,compared to the research on the effects of PD-1/PD-L1 on tumors,there is relatively little research on PD-1/PD-L1 in inflammation.There is no corresponding drug for clinical treatment,which requires much basic experimental research support.