Table_4_TERT Mutation Is Accompanied by Neutrophil Infiltration and Contributes to Poor Survival in Isocitrate Dehydrogenase Wild-Type Glioma.DOCX

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 TERT promoter mutation status which could improve prognostic prediction in IDHwt. TERT mutation status, IDH 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. TERT mutation is preferentially present in glioblastoma and IDH-wt gliomas and is associated with poor prognosis. Moreover, TERT 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. TERT 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（telomerase reverse transcriptase, TERT）启动子突变已被证实为异柠檬酸脱氢酶野生型（isocitrate dehydrogenase wild-type, IDHwt）胶质瘤患者的不良预后标志物。本研究旨在探究TERT启动子突变状态的免疫调控作用，以优化IDHwt胶质瘤的预后预测效能。研究从癌症基因组图谱（Cancer Genome Atlas）队列中纳入614例胶质瘤病例、中国胶质瘤基因组图谱（Chinese Glioma Genome Atlas）队列中纳入325例胶质瘤病例，获取其TERT突变状态、IDH突变状态及1p-19q共缺失状态数据，并额外纳入49例临床胶质瘤组织样本的同类信息进行分析。结果显示，TERT突变更易发生于胶质母细胞瘤及IDH野生型胶质瘤中，且与不良预后显著相关。此外，TERT突变与中性粒细胞浸润水平及中性粒细胞趋化因子的表达密切相关，这可能部分解释了IDH野生型胶质瘤患者预后不佳的原因。进一步分析发现，IDH野生型胶质瘤患者的外周血中性粒细胞并未出现数量升高，提示肿瘤微环境中的浸润性中性粒细胞或由细胞因子趋化募集而来。本研究提出，TERT突变可能是IDH野生型胶质瘤功能失调性免疫微环境形成的分子驱动因素，其可作为潜在的免疫治疗靶点，用于优化胶质瘤免疫治疗的联合方案及患者筛选策略。