Deciphering Translational Insights from Mouse Model to Human Tumors Using Imaging Mass Cytometry 2259293

Abstract Introduction Glioblastoma (GBM) is highly aggressive disease due to rapid growth, therapeutic resistance and recurrence. Its spatial heterogeneity creates distinct niches, including necrotic cores, vascular regions and immune-suppressed areas, complicating treatment. Mouse models are widely used in neuro research due to conserved brain architecture enabling tissue-wide spatial studies. However, translating insights to humans requires high-resolution, multiplexed spatial technologies with high data quality. Imaging Mass Cytometry™ (IMC™) technology allows quantitative spatial proteomic analysis without issues like autofluorescence or tissue damage. Methods In this study, the Hyperion™ XTi Imaging System was used with 40-plus-marker panels combining mouse and human immuno-oncology and neurophenotyping kits to analyze spatial biology in mouse and human GBM tissues, respectively. Data analysis with pixel clustering and single-cell quantification identified conserved spatial features across species, revealing a heterogeneous tumor microenvironment (TME). Results Conserved spatial features were detected in both human and mouse GBM samples, highlighting striking heterogeneity. Multiple GBM subregions were located in both mouse and human tissues containing replicating Olig-2+ cells. A high concentration of infiltrated immune cells was present in human and mouse GBM, although spatial distribution was distinct. Spatial segmentation quantitatively distinguished tumor subregions, including differentiated tumor cells, immune hot and cold zones, stromal compartments, angiogenic vasculature and extracellular matrix. Conclusion The study demonstrates the utility of IMC technology in bridging mouse-human translational research by enabling cross-species validation of TME markers. Access to this information facilitates accelerated discovery of biomarker and targets for cancer therapies. For Research Use Only. Not for use in diagnostic procedures. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)