Journal
ACTA NEUROPATHOLOGICA COMMUNICATIONS
Volume 9, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40478-020-01115-0
Keywords
Glioblastoma; Blood vessels; Microglia; Macrophages; Astrocytes; T cells; Endothelium; Basement membrane; Tumor microenvironments
Categories
Funding
- Spanish Ministry of Economy and Competitiveness
- European Regional Development Fund (Fondo Europeo de Desarrollo Regional, FEDER) [RYC-2010-06729, SAF2013-45178-P, PEJ-2014-P00015, SAF2015-64123-P]
- Generalitat de Catalunya [2014 SGR-984]
- Spanish Ministry of Science, Innovation and Universities [PGC2018-096003-B-I00]
- Asociacion Espanola Contra el Cancer (AECC)
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This study provides an in-depth analysis of the cellular composition and microenvironment of human glioblastoma, revealing its structural and biological characteristics. The critical association between tumor cells and neo-vascular niche, as well as the relationship between T cell infiltration and tumor proliferation, were highlighted. The research also discovered distinct cell phenotypes in tumor nests and surrounding tissues.
The cellular complexity of glioblastoma microenvironments is still poorly understood. In-depth, cell-resolution tissue analyses of human material are rare but highly necessary to understand the biology of this deadly tumor. Here we present a unique 3D visualization revealing the cellular composition of human GBM in detail and considering its critical association with the neo-vascular niche. Our images show a complex vascular map of human 3D biopsies with increased vascular heterogeneity and altered spatial relationship with astrocytes or glioma-cell counterparts. High-resolution analysis of the structural layers of the blood brain barrier showed a multilayered fenestration of endothelium and basement membrane. Careful examination of T cell position and migration relative to vascular walls revealed increased infiltration corresponding with tumor proliferation. In addition, the analysis of the myeloid landscape not only showed a volumetric increase in glioma-associated microglia and macrophages relative to GBM proliferation but also revealed distinct phenotypes in tumor nest and stroma. Images and data sets are available on demand as a resource for public access.
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