蛋白酶体β亚基8在肿瘤发生发展中的作用及其预测免疫治疗疗效的价值

The role of proteasome subunit beta 8 in tumorigenesis and development and its value in predicting effects of immunotherapy

蛋白酶体β亚基 8(proteasome subunit beta 8,PSMB8)是免疫蛋白酶体的组成部分,在细胞内蛋白质降解、细胞内环境稳定维持和内源性抗原提呈方面发挥重要作用.随着分子检测技术的革新和细胞系实验的进行,PSMB8 在基因组学、表观组学以及转录组学等水平上与肿瘤发生发展之间的密切关系逐渐被揭示,这使得PSMB8 成为肿瘤治疗的靶点并有望成为预测抗肿瘤治疗疗效的生物标志物.随着免疫检查点抑制剂的应用,恶性肿瘤的治疗进入了免疫治疗时代.然而,并非所有接受免疫治疗的患者均能从治疗中获益,因此许多生物标志物被探索并用于适宜治疗人群的筛选.目前,常用的生物标志物有程序性死亡配体1、肿瘤突变负荷等,但这些标志物不能完全解释免疫治疗的临床获益,因此探索更多生物标志物对于精准医疗有着重要的意义.考虑到免疫检查点抑制剂的作用机制在于重新活化免疫细胞,因此需要患者有一定的基础免疫条件,故PSMB8 作为抗原提呈的重要参与分子可能具有预测免疫治疗疗效的价值.文章将结合近年来生物信息学分析文献和细胞及动物实验文献,解析PSMB8在肿瘤发生发展中的作用及对免疫治疗疗效的预测价值.

Proteasome subunit beta 8(PSMB8)is a component of the immunoproteasome,which plays an important role in both degradation of proteins to maintain intracellular homeostasis and presentation of endogenous antigens.With the development of molecular detection technology and cell experiment,the relationship between PSMB8 and tumorigenesis as well as tumor development has been gradually revealed in genomic,epigenomic and transcriptomic levels.Therefore,PSMB8 has become both a treatment target and a prognostic biomarker in anti-tumor therapy.Recently,many immune checkpoint inhibitors(ICIs)have been developed and employed,the treatment of malignant tumors has entered the era of immunotherapy.However,not all patients receiving ICIs could benefit from them,and many biomarkers were explored to screen suitable populations.Currently,the commonly used biomarkers include programmed death ligand 1(PD-L1),tumor mutation burden(TMB),etc.Nevertheless,these markers cannot fully explain the clinical benefits.To reach precision medicine,it is necessary to explore more biomarkers for patients receiving ICIs.Considering that the mechanism of ICIs is to reactivate immune cells,PSMB8 might have potential value in predicting ICIs'effects,which attributes to its role in processing antigen and promoting infiltration of immune cells.In this article,we will review recent bioinformatic and experimental researches on PSMB8 and analyze the role of PSMB8 in tumorigenesis as well as its predictive value of ICIs'effects.