Wenying Wang, Tianran Li, Yue Cheng, Fei Li, Shuhong Qi, Min Mao, Jingjing Wu, Qing Liu, Xiaoning Zhang, Xuegang Li, Lu Zhang, Haoyue Qi, Lan Yang, Kaidi Yang, Zhicheng He, Shuaishuai Ding, Zhongyi Qin, Ying Yang, Xi Yang, Chunhua Luo, Ying Guo, Chao Wang, Xindong Liu, Lei Zhou, Yuqi Liu, Weikai Kong, Jingya Miao, Shuanghui Ye, Min Luo, Lele An, Lujing Wang, Linrong Che, Qin Niu, Qinghua Ma, Xia Zhang, Zhihong Zhang, Rong Hu, Hua Feng, Yi-Fang Ping, Xiu-Wu Bian, Yu Shi
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...
April 16, 2024: Cancer Cell