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Updated: Sep 9, 2025
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Spatial profiling of longitudinal glioblastoma reveals consistent changes in cellular architecture, post-treatment
Shoaib Ajaib1, Joshua Winter-Luke1, Richard J Digby2,1
1Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Background:
Glioblastoma (GBM), the most aggressive adult brain cancer, comprises a complex tumor microenvironment (TME) with diverse cellular interactions that drive progression and pathobiology. The aim of this study was to understand how these spatial patterns and interactions evolve with treatment.
Methods:
To explore these relationships, we employed imaging mass cytometry to measure the expression of 34 protein markers, enabling the identification of GBM-specific cell types and their interactions at the single-cell protein level in paired primary (pre-treatment) and recurrent (post-treatment) GBM samples from five patients.
Results:
We find a significant post-treatment increase in normal brain cells alongside a reduction in vascular cells. Moreover, despite minimal overall change in cellular diversity, interactions among astrocytes, oligodendrocytes, and vascular cells increase post-treatment, suggesting reorganization of the TME. The GBM TME cells form spatially organized layers driven by hypoxia pre-treatment, but this influence diminishes post-treatment, giving way to less organized layers with organization driven by reactive astrocytes and lymphocytes.
Conclusions:
These findings provide insight into treatment-induced shifts in GBM's cellular landscape, highlighting aspects of the evolving TME that appear to facilitate recurrence and are, therefore, potential therapeutic targets.
