Tumor-associated monocytes promote mesenchymal transformation through EGFR signaling in glioma

被引：14
作者：
Chen, Yiyun [1 ,2 ,3 ]
Huo, Ran [4 ,5 ]
Kang, Weirong [6 ,7 ]
Liu, Yuwei [6 ,7 ]
Zhao, Zheng [1 ,2 ,8 ]
Fu, Weilun [4 ,5 ]
Ma, Ruochen [1 ,2 ]
Zhang, Xiaomeng [1 ,2 ]
Tang, Jihong [1 ,2 ]
Zhu, Zhihan [1 ,2 ]
Lyu, Qingyang [6 ]
Huang, Yi [6 ]
Yan, Mengli [1 ,2 ]
Jiang, Biaobin [1 ,2 ]
Chai, Ruichao [1 ,2 ,3 ,8 ]
Bao, Zhaoshi [4 ,5 ]
Hu, Zheng [3 ,9 ]
Wang, Weiping [6 ,7 ]
Jiang, Tao [4 ,5 ,8 ]
Cao, Yong [4 ,5 ]
Wang, Jiguang [1 ,2 ,3 ,10 ]
机构：
[1] TheHong Kong Univ Sci & Technol, Dept Chem & Biol Engn, Div Life Sci, Hong Kong, Peoples R China
[2] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Hong Kong, Peoples R China
[3] HKUST Shenzhen Hong Kong Collaborat Innovat Res In, SIAT HKUST Joint Lab Cell Evolut & Digital Hlth, Futian, Shenzhen, Peoples R China
[4] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
[5] China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China
[6] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Hong Kong, Peoples R China
[7] Univ Hong Kong, Dr Li Dak Sum Res Ctr, Lab Mol Engn & Nanomed, Hong Kong, Peoples R China
[8] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China
[9] Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, CAS Key Lab Quantitat Engn Biol, Shenzhen, Peoples R China
[10] InnoHK, Hong Kong Ctr Neurodegenerat Dis, Hong Kong, Peoples R China
来源：
CELL REPORTS MEDICINE | 2023年 / 4卷 / 09期
基金：
中国国家自然科学基金;
关键词：
CELL LUNG-CANCER; RECURRENT GLIOBLASTOMA; AMPHIREGULIN; EPIREGULIN; QUANTIFICATION; HETEROGENEITY; ANTIBODY; NETWORK; DISEASE;
D O I：
10.1016/j.xcrm.2023.101177
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 3 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.
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页数：24
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