脑免疫组织在胶质瘤演变过程中的作用仍不清楚。我们对11名患者的胶质瘤微环境中的免疫细胞和相应的外周血进行了分析。胶质母细胞瘤表现出特定的浸润血源单核细胞，这些细胞表达表皮生长因子受体（EGFR）配体EREG和AREG，被称为肿瘤相关单核细胞（TAMo）。TAMo的浸润与EGFR基因改变互斥（p = 0.019），而与间质亚型共存（p = 4.7 × 10-7），并标志着较差的预后（两个队列中分别为p = 0.004和0.032）。对最初-复发胶质瘤对的演化分析和多中心胶质母细胞瘤的单细胞研究揭示了TAMo升高与胶质瘤间质转化之间的关联。进一步的分析确定了FOSL2作为TAMo主控因子，并证明了FOSL2-EREG/AREG-EGFR信号轴在体外促进胶质瘤的侵袭。总之，我们在肿瘤微环境中鉴定了TAMo，并揭示其在激活EGFR信号传导以塑造胶质瘤演变过程中的推动作用。版权所有©2023年作者。Elsevier Inc.保留所有权利。

The role of brain immune compartments in glioma evolution remains elusive. We profile immune cells in glioma microenvironment and the matched peripheral blood from 11 patients. Glioblastoma exhibits specific infiltration of blood-originated monocytes expressing epidermal growth factor receptor (EGFR) ligands EREG and AREG, coined as tumor-associated monocytes (TAMo). TAMo infiltration is mutually exclusive with EGFR alterations (p = 0.019), while co-occurring with mesenchymal subtype (p = 4.7 × 10-7) and marking worse prognosis (p = 0.004 and 0.032 in two cohorts). Evolutionary analysis of initial-recurrent glioma pairs and single-cell study of a multi-centric glioblastoma reveal association between elevated TAMo and glioma mesenchymal transformation. Further analyses identify FOSL2 as a TAMo master regulator and demonstrates that FOSL2-EREG/AREG-EGFR signaling axis promotes glioma invasion in vitro. Collectively, we identify TAMo in tumor microenvironment and reveal its driving role in activating EGFR signaling to shape glioma evolution.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.