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Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Identification of hypoxic macrophages in glioblastoma: Unveiling therapeutic insights from tumour microenvironment
Zhen Qin1, Xiu-Wu Bian1,2, Yu Shi1,2
1Institute of Pathology and Glioma Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), and the Key Laboratory of Tumour Immunopathology, The Ministry of Education of China, Chongqing, P. R. China.
Abstract:
Tumor-associatedmacrophages (TAMs) exhibit remarkable heterogeneity in glioblastoma. Spatially resolved single-cell transcriptomic studies identified a monocyte-derived TAM subset localized in the peri-necrotic niche, driven by hypoxic cues to acquire ahypoxia response signature. These hypoxia-TAMs destabilize endothelial adherens junctions through adrenomedullin paracrine signaling, promoting the formation of hyperpermeable neovasculature that impedes drug delivery. Blocking adrenomedullin produced by hypoxia-TAMs restores vascular integrity, increases drug deliveryinto tumors, and provides combinatorial therapeutic benefits. Here we discuss the heterogeneity of TAMs regarding functional states and locations in glioblastomas, and propose future directions for studying the temporospatial dynamics of multifaceted TAM. HIGHLIGHTS: Single-cell omics reveal a functionally and spatially distinct hypoxia-TAM subset in glioblastoma. Adrenomedullin secreted by hypoxia-TAM destabilizes tumor vasculature and its blockade enhances vessel integrity and drug delivery.
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