胶质瘤干细胞（GSC）的自我更新是胶质母细胞瘤（GBM）治疗耐药和复发的原因。肿瘤坏死因子 α (TNFα) 和 TNF 信号通路在临床前模型和肿瘤患者中显示出抗肿瘤活性。然而，根据胶质瘤基因组图谱数据库，TNFα对胶质瘤临床预后没有显着意义。本研究旨在探讨肿瘤微环境中的TNFα是否维持GSC的自我更新并导致胶质瘤患者预后较差。采用空间转录组学、免疫印迹、球体形成实验、极限稀释和基因表达分析来确定TNFα对胶质瘤患者预后的作用。 GSC 的自我更新。采用质谱、RNA测序检测、生物信息分析、qRT-RNA、免疫荧光、免疫组化、单细胞RNA测序、体外和体内模型揭示TNFα诱导GSC自我更新的机制。低水平的TNFα显示对 GSC 自我更新有促进作用，且神经胶质瘤预后较差。从机制上讲，Vasorin (VASN) 通过增强糖酵解介导 TNFα 诱导的自我更新。糖酵解产生的乳酸抑制肿瘤相关巨噬细胞（TAM）分泌TNFα，使TNFα维持在较低水平。VASN介导的TNFα诱导的GSC自我更新为内源性TNFα作用于GBM的失败提供了可能的解释。结合靶向 VASN 和 TNFα 抗肿瘤作用可能是治疗 GBM 的有效方法。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Self-renewal of glioma stem cells (GSCs) is responsible for glioblastoma (GBM) therapy-resistant and recurrence. Tumor necrosis factor α (TNFα) and TNF signaling pathway display an antitumor activity in preclinical models and in tumor patients. However, TNFα exhibits no significance for glioma clinical prognosis based on Glioma Genome Atlas database. This study aimed to explore whether TNFα of tumor microenvironment maintains self-renewal of GSCs and promotes worse prognosis in glioma patient.Spatial transcriptomics, immunoblotting, sphere formation assay, extreme limiting dilution, and gene expression analysis were used to determine the role of TNFα on GSC's self-renewal. Mass spectrometry, RNA-sequencing detection, bioinformatic analyses, qRT-RNA, immunofluorescence, immunohistochemistry, single cell RNA sequencing, in vitro and in vivo models were used to uncover the mechanism of TNFα-induced GSC self-renewal.Low level of TNFα displays a promoting effect on GSC self-renewal and worse glioma prognosis. Mechanistically, Vasorin (VASN) mediated TNFα-induced self-renewal by potentiating glycolysis. Lactate produced by glycolysis inhibits the TNFα secretion of tumor-associated macrophages (TAMs) and maintains TNFα in a low level.TNFα-induced GSC self-renewal mediated by VASN provides a possible explanation for the failures of endogenous TNFα effect on GBM. Combination of targeting VASN and TNFα anti-tumor effect may be an effective approach for treating GBM.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.