Spatial profiling of longitudinal glioblastoma reveals consistent changes in cellular architecture, post-treatment.
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All Authors
Ajaib, S.
Winter-Luke, J.
Digby, RJ.
Pollock, S.
Hemmings, G.
Gusnanto, A.
Chakrabarty, A.
Ismail, A.
Wilson, E.
Hunter, B.
LTHT Author
Chakrabarty, Aruna
Ismail, Azzam
Ismail, Azzam
LTHT Department
Pathology
Histopathology
Histopathology
Non Medic
Publication Date
2025
Item Type
Journal Article
Language
Subject
Subject Headings
Abstract
BACKGROUND: Glioblastoma (GBM), the most aggressive adult brain cancer, comprises a complex tumour 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 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 reorganisation 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 organised layers with organisation 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.
Journal
Neuro-Oncology