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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; Yang, Lan; Yang, Kaidi; He, Zhicheng; Ding, Shuaishuai; Qin, Zhongyi; Yang, Ying; Yang, Xi; Luo, Chunhua; Guo, Ying; Wang, Chao; Liu, Xindong; Zhou, Lei; Liu, Yuqi; Kong, Weikai; Miao, Jingya; Ye, Shuanghui; 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.
Affiliation
  • Wang W; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Li T; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Cheng Y; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Li F; Department of Neurosurgery and Glioma Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China.
  • Qi S; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, and MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan 430074, Hubei, P.R. China.
  • Mao M; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Wu J; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Liu Q; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Zhang X; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Li X; Department of Neurosurgery and Glioma Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China.
  • Zhang L; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Qi H; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Yang L; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Yang K; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • He Z; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Ding S; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Qin Z; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China; Department of Gastroenterology, Chongqing Key Laborat
  • Yang Y; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Yang X; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Luo C; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Guo Y; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Wang C; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Liu X; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Zhou L; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Liu Y; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Kong W; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Miao J; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Ye S; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Luo M; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • An L; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Wang L; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Che L; Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing 400042, P.R. China.
  • Niu Q; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Ma Q; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Zhang X; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
  • Zhang Z; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, and MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan 430074, Hubei, P.R. China.
  • Hu R; Department of Neurosurgery and Glioma Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China.
  • Feng H; Department of Neurosurgery and Glioma Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China.
  • Ping YF; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China; Chongqing Advanced Pathology Research Institute, Jinf
  • Bian XW; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China; Chongqing Advanced Pathology Research Institute, Jinf
  • Shi Y; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China; Chongqing Advanced Pathology Research Institute, Jinf
Cancer Cell ; 42(5): 815-832.e12, 2024 May 13.
Article in En | MEDLINE | ID: mdl-38640932
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 ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Glioblastoma / Adrenomedullin / Tumor-Associated Macrophages Limits: Animals / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2024 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Glioblastoma / Adrenomedullin / Tumor-Associated Macrophages Limits: Animals / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2024 Document type: Article Country of publication: United States