Expression of the immunoproteasome subunit β5i in non-small cell lung carcinomas
Expression of the immunoproteasome subunit β5i in non-small cell lung carcinomas
复制标题
DOI：
10.1136/jclinpath-2020-206618
复制
发表时间：
2021-05-01
影响因子：
3.4
通讯作者：
Kasahara, Masanori
中科院分区：
文献类型：
--
作者：
Kiuchi, Takayuki;Tomaru, Utano;Kasahara, Masanori
目的免疫蛋白酶体是一种特殊的蛋白酶体异构体，其蛋白水解活性增强了抗原肽的产生，这些抗原肽由主要的组织相容性复合体I类分子呈递给CD8(+) T细胞。在生理上，它在免疫细胞中大量表达，并在体细胞中被细胞因子，特别是干扰素诱导。最近，免疫蛋白酶体的可变表达已在不同类型的癌症中得到证实。然而，免疫蛋白酶体在恶性肿瘤中表达的临床意义尚不清楚。在这项研究中，我们对非小细胞肺癌（nsclc）中免疫蛋白酶体亚单位β 5i进行了临床病理评估。方法收集155例非小细胞肺癌患者的肿瘤组织，免疫组化分析β 5i与患者预后的关系。结果β 5i高表达在约20%的非小细胞肺癌中发现，在腺癌亚群中发现的频率更高（40%）。β 5i的高表达与pi期至II期腺癌患者更好的5年相对生存率相关，也是腺癌患者重要且独立的有利预后因素。此外，当我们对非小细胞肺癌细胞系进行体外分析时，免疫蛋白酶体特异性抑制剂ONX0914和蛋白酶体抑制剂MG132联合治疗可增强表达β 5i的非小细胞肺癌细胞系的细胞死亡。结论免疫蛋白酶体的表达可作为非小细胞肺癌的预后因素和潜在的治疗靶点。由于免疫蛋白酶体在抗原呈递中起着至关重要的作用，进一步的研究可能有助于为抗癌免疫治疗的治疗策略提供必要的知识。
AimThe immunoproteasome is a specific proteasome isoform whose proteolytic activity enhances the generation of antigenic peptides to be presented by major histocompatibility complex class I molecules to CD8(+) T cells. Physiologically, it is expressed abundantly in immune cells and is induced in somatic cells by cytokines, especially interferon-gamma. Recently, variable expression of immunoproteasomes has been demonstrated in different types of cancers. However, the clinical significance of immunoproteasome expression in malignant tumours is poorly understood. In this study, we performed clinicopathological evaluation of immunoproteasome subunit beta 5i in non-small cell lung carcinomas (NSCLCs).MethodsTumour tissues were collected from 155 patients with NSCLCs, and immunohistochemical analysis for beta 5i was performed in relation to the prognosis of patients.ResultsHigh expression of beta 5i was found in about 20% of all NSCLCs and was found significantly more frequently (40%) in the adenocarcinoma subset. High expression of beta 5i was associated with a better 5-year relative survival rate in patients with pStage I to II adenocarcinoma and was also a significant and independent favourable prognostic factor in adenocarcinoma patients. In addition, when we performed in vitro analysis using NSCLC cell lines, combined treatment with the immunoproteasome-specific inhibitor ONX0914 and the proteasome inhibitor MG132 enhanced cell death in beta 5i-expressing NSCLC cell lines.ConclusionThe expression of immunoproteasome can be explored as both a prognostic factor and a potential therapeutic target in NSCLCs. Since immunoproteasomes have crucial role in the antigen presentation, further studies may help to provide essential knowledge for therapeutic strategies in anticancer immunotherapy.