Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma
Vidhya M Ravi1, Paulina Will2, Jan Kueckelhaus3
1Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany; Center of Advanced Surgical Tissue Analysis (CAST), University of Freiburg, Freiburg, Germany.
Glioblastoma tumors adapt to their environment, showing spatial organization of cell states. This dynamic adaptation, driven by inflammation and metabolism, influences tumor evolution and subclone selection.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Systems Biology
Background:
- Glioblastomas exhibit significant subclonal diversity and dynamic adaptation.
- The origins of spatial reorganization within glioblastomas are not well understood.
- Understanding tumor microenvironment interactions is crucial for glioblastoma research.
Purpose of the Study:
- To investigate the spatial organization and adaptive mechanisms of glioblastomas.
- To identify the environmental factors driving tumor adaptation and evolution.
- To model glioblastoma stem cell behavior in response to varying microenvironments.
Main Methods:
- Spatially resolved transcriptomics, metabolomics, and proteomics were employed.
- Integration of metabolic imaging and imaging mass cytometry.
- In vitro and in vivo modeling of glioblastoma stem cells in diverse environments.
Main Results:
- Glioblastomas are spatially segregated by lineage states, adapting to inflammatory and metabolic stimuli.
- Tumor-host interdependence creates spatially exclusive adaptive transcriptional programs.
- Environmental stress drives selection pressure, leading to spatially cohesive subclones with reactive programs.
Conclusions:
- Glioblastoma transcriptional states arise from dynamic adaptation to environmental cues.
- Spatial organization and environmental interactions are key drivers of glioblastoma heterogeneity and progression.
- This study provides insights into glioblastoma's adaptive nature and potential therapeutic targets.
