Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization

Wang, Wenying; Li, Tianran; Cheng, Yue; Li, Fei; Qi, Shuhong; Mao, Min; Wu, Jingjing; Liu, Qing; Zhang, Xiaoning; Li, Xuegang; Zhang, Lu; Qi, Haoyue; Lan, Yang; Yang, Kaidi; He, Zhicheng; Ding, Shuaishuai; Qin, Zhongyi; Yang, Ying; Yang, Xi; Luo, Chunhua; Guo, Ying; Wang, Chao; Liu, Xindong; Zhou, L.; Liu, Yuqi; Kong, Weikai; Miao, Jingya; Ye, Shuang-Hui; Luo, Min; An, Lele; Wang, Lujing; Che, Linrong; Niu, Qin; Ma, Qinghua; Zhang, Xia; Zhang, Zhihong; Hu, Rong; Feng, Hua; Ping, Yi‐Fang; Bian, Xiu‐Wu; Shi, Yu

doi:10.1016/j.ccell.2024.03.013

articleCancer CellApr 18, 2024HYBRID OA

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization

WWWenying Wang TLTianran Li YCYue Cheng FLFei Li SQShuhong Qi

Army Medical University · Southwest Hospital · +4 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic…

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Topics & keywords

Topics

Keywords

Cancer research
Hypoxia (environmental)
Paracrine signalling
Adrenomedullin
Biology
Glioma
Transcriptome
Tumor microenvironment

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