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Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2?.

ABSTRACT: Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-?-dependent transcriptional activation of hypoxia-inducible factor-2?. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors.

SUBMITTER: Wang Q

PROVIDER: S-EPMC5805734 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α.

Wang Qirui Q He Zhenqiang Z Huang Menggui M Liu Tianrun T Wang Yanling Y Xu Haineng H Duan Hao H Ma Peihong P Zhang Lin L Zamvil Scott S SS Hidalgo Juan J Zhang Zhenfeng Z O'Rourke Donald M DM Dahmane Nadia N Brem Steven S Mou Yonggao Y Gong Yanqing Y Fan Yi Y

Nature communications 20180208 1

Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating fact ...[more]

PMID: 29422647

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Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2?.

Publications

Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α.

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