肿瘤细胞核程序性死亡配体1的研究进展

Progress in the nuclear programmed cell death ligand 1 in nucleus tumor cell

程序性死亡配体1(Programmed cell death ligand 1,PD-L1)是一种Ⅰ型跨膜蛋白,与程序性死亡受体1(Programmed cell death protein 1,PD-1)结合,诱导肿瘤免疫逃逸。靶向PD-1/PD-L1通路的临床免疫治疗逐渐开展,但在部分肿瘤治疗中未能取得满意的效果。近年来研究发现PD-L1不仅定位于细胞膜,还定位在细胞质、细胞核或者细胞外,并且发挥相应的功能。本文结合近年来国内外的研究,从细胞核PD-L1(Nuclear PD-L1,nPD-L1)的表达、转运、功能、检测及临床意义等方面进行综述。文献复习结果表明,PD-L1在多种肿瘤细胞核中表达。在外界刺激因素作用下,PD-L1可通过核转运蛋白、信号转导及转录激活蛋白3、蛋白激酶B、细胞外调节蛋白激酶等多个信号通路转运至细胞核内,调控肿瘤增殖和死亡、免疫、血管及干细胞生成。通过免疫组化等方法检测nPD-L1的表达,对肿瘤诊断、治疗、预后、监测及随访均有重要意义,nPD-L1有可能成为新的治疗靶点并进入临床应用。

Programmed cell death ligand 1(PD-L1)is a type I transmembrane protein that binds to programmed cell death protein 1(PD-1)to induce tumor immune escape.Clinical immunotherapy targeting the PD-1/PD-L1 pathway has been gradually developed.However,satisfactory results have not been achieved in some tumor treatment.Recent studies have found that PD-L1 is not only localized in the cell membrane,but also appears in the cytoplasm,the nucleus,or outside the cell with corresponding functions.This paper summarizes the expression,transport,function,detection and clinical significance of nuclear PD-L1(nPD-L1),based on recent domestic and foreign research literature.The results of literature review show that PD-L1 is expressed in a variety of tumor nuclei.Under the action of external stimuli,PD-L1 can be transported to the nucleus through several signaling pathways such as Karyopherin,signal transducer and activator of transcription 3,protein kinase B,extracellular regulated protein kinases,and regulate the proliferation and death,immunity,blood vessels and stem cell generation of tumor.Detection of the expression of nPD-L1 by immunohistochemistry and other methods is of great significance for the diagnosis,treatment,prognosis,monitoring and follow-up of tumors,and nPD-L1 may become a new therapeutic target and enter clinical application.