Gao Mengqi, Lin Yi, Liu Xing, Zhao Zheng, Zhu Zhiyuan, Zhang Hongbo, Ban Yunchao, Bie Yanan, He Xiaozheng, Sun Xiang, Zhang Shizhong
Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Functional Neurosurgery, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
Front Cell Dev Biol. 2021 Apr 30;9:654407. doi: 10.3389/fcell.2021.654407. eCollection 2021.
Mutation of the telomerase reverse transcriptase (TERT) promoter has been demonstrated as an unfavorable prognostic marker in patients with isocitrate dehydrogenase wild-type (IDHwt) glioma. This study aimed to investigate the immune role of promoter mutation status which could improve prognostic prediction in IDHwt. mutation status, mutation, and 1p-19q codeletion status data were obtained from 614 glioma cases from the Cancer Genome Atlas, and 325 cases from the Chinese Glioma Genome Atlas. The same information was obtained from 49 clinical glioma tissues. mutation is preferentially present in glioblastoma and IDH-wt gliomas and is associated with poor prognosis. Moreover, mutation was associated with infiltration of neutrophils and expression of neutrophil chemokines. which might partially contribute to the poor outcome in IDH-wt glioma. Furthermore, patients with IDH-wt glioma did not harbor increased peripheral neutrophils, implying that the infiltrated neutrophil in the tumor environment might due to cytokine chemotaxis. In this study, we hereby propose that TERT mutation might be a molecular driver of the dysfunctional immune microenvironment in IDH-wt glioma. mutation may be a potential immune therapeutic target for optimizing treatment combinations and patient selection for glioma immunotherapy.
端粒酶逆转录酶(TERT)启动子突变已被证明是异柠檬酸脱氢酶野生型(IDHwt)胶质瘤患者不良预后的标志物。本研究旨在探讨TERT启动子突变状态的免疫作用,以改善IDHwt胶质瘤患者的预后预测。从癌症基因组图谱(Cancer Genome Atlas)的614例胶质瘤病例以及中国胶质瘤基因组图谱(Chinese Glioma Genome Atlas)的325例病例中获取TERT启动子突变状态、IDH突变和1p-19q共缺失状态数据。从49例临床胶质瘤组织中获取相同信息。TERT启动子突变优先存在于胶质母细胞瘤和IDH野生型胶质瘤中,并与预后不良相关。此外,TERT启动子突变与中性粒细胞浸润和中性粒细胞趋化因子的表达相关,这可能部分导致IDH野生型胶质瘤的不良预后。此外,IDH野生型胶质瘤患者外周血中性粒细胞并未增加,这意味着肿瘤环境中浸润的中性粒细胞可能是由于细胞因子趋化作用。在本研究中,我们特此提出TERT突变可能是IDH野生型胶质瘤免疫微环境功能失调的分子驱动因素。TERT启动子突变可能是优化胶质瘤免疫治疗联合方案和患者选择的潜在免疫治疗靶点。