Three-dimensional vascular microenvironment landscape in human glioblastoma

Acta Neuropathol Commun. 2021 Feb 12;9(1):24. doi: 10.1186/s40478-020-01115-0.

Abstract

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.

Keywords: Astrocytes; Basement membrane; Blood vessels; Endothelium; Glioblastoma; Macrophages; Microglia; T cells; Tumor microenvironments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / pathology
  • Glioblastoma / blood supply*
  • Glioblastoma / pathology
  • Humans
  • Imaging, Three-Dimensional / methods*
  • Microvascular Density*
  • Tumor Microenvironment*