肿瘤相关单核细胞通过 EGFR 信号在神经胶质瘤中促进间充质转化。
Tumor-associated monocytes promote mesenchymal transformation through EGFR signaling in glioma.
机构信息
Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong SAR, China; SIAT-HKUST Joint Laboratory of Cell Evolution and Digital Health, HKUST Shenzhen-Hong Kong Collaborative Innovation Research Institute, Futian, Shenzhen, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.
出版信息
Cell Rep Med. 2023 Sep 19;4(9):101177. doi: 10.1016/j.xcrm.2023.101177. Epub 2023 Aug 30.
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) 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.
脑免疫区室在神经胶质瘤演进中的作用仍不清楚。我们对 11 名患者的神经胶质瘤微环境和配对的外周血中的免疫细胞进行了分析。胶质母细胞瘤表现出特异性浸润表达表皮生长因子受体（EGFR）配体 EREG 和 AREG 的血源性单核细胞，被称为肿瘤相关单核细胞（TAMo）。TAMo 的浸润与 EGFR 改变互斥（p = 0.019），同时与间充质亚型共发生（p = 4.7×10）并提示预后较差（在两个队列中 p = 0.004 和 0.032）。对初始-复发性神经胶质瘤对和多中心胶质母细胞瘤的单细胞研究的进化分析表明，TAMo 升高与神经胶质瘤间充质转化之间存在关联。进一步的分析确定 FOSL2 是 TAMo 的主要调控因子，并证明 FOSL2-EREG/AREG-EGFR 信号轴促进了体外神经胶质瘤的侵袭。总之，我们在肿瘤微环境中鉴定出 TAMo，并揭示了其在激活 EGFR 信号以塑造神经胶质瘤演进中的驱动作用。
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