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.
Highlights
Despite the recent progress of successful immunotherapeutic options for many types of cancers, glioblastoma (GBM) remains incurable [9, 16]
Results for Cluster of differentiation 31 (CD31) surface area and multiple comparisons between cellularity, vessel continuity, Collagen IV or Type-IV colla‐ gen (COL-IV) and CD31 surface areas, colocalization and Glial fibrillary acidic proteinCOL-IV (GFAP) surface area, derive from a sample set stained for COL-IV, CD31 and GFAP and counterstained with DAPI with 24 total data points for each variable, six for normal tissue and 18 for tumor tissue blocks
Total T cell counts, and T cell extravasation and migration data were drawn from a sample pool immunostained for CD31, Cluster of differentiation 3 (CD3) and GFAP and counterstained with DAPI
Summary
Despite the recent progress of successful immunotherapeutic options for many types of cancers, glioblastoma (GBM) remains incurable [9, 16]. The aggressive nature of this brain tumor causes a rapid and severe spread of malignant cells in brain tissue with irreparable loss. The extremely complex cellular structure of GBM that enables this invasiveness is still poorly understood and deserves a detailed microanatomical study to comprehend its biology. Indepth studies of the GBM microenvironment performed in human tissue are limited and many conclusions are drawn from animal models or in vitro simulations [26, 34]. High-resolution microstructural studies of patient samples are critical to understand cellular composition as well as how the tumor microenvironment is established in its real scenario. It is crucial to consider the three-dimensional architectural preservation of the human tissue including, the parenchyma and the vascular niche so as to understand the full complexity of the tumor
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