第三军医大学时雨等研究人员合作发现，胶质母细胞瘤中缺氧巨噬细胞的鉴定具有血管正常化的治疗潜力。该项研究成果于2024年4月18日在线发表在《癌细胞》杂志上。

研究人员表示，Mo-TAM以显著的异质性密集浸润弥漫性胶质瘤。

附：英文原文

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

Author: 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

Issue&Volume: 2024-04-18

Abstract: Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffusegliomas with remarkable heterogeneity. Using single-cell transcriptomics, we charta spatially resolved transcriptional landscape of Mo-TAMs across 51 patients withisocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterizea Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxicniche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelialadherens junctions by activating adrenomedullin paracrine signaling, thereby stimulatinga hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts.Accordingly, genetic ablation or pharmacological blockade of adrenomedullin producedby Hypoxia-TAM restores vascular integrity, improves intratumoral concentration ofthe anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits.Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive oftumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffusegliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

DOI: 10.1016/j.ccell.2024.03.013

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00119-3