{
  "abstract": "Background Human brain neoplasms, such as glioblastoma (GBM), are among the most lethal malignancies, characterized by rapid progression, therapeutic resistance and recurrence. Their complex spatial heterogeneity features compartmentalized niches like necrotic cores, tumor vascularization and suppressed immune cells, which hinders treatment efficacy. Mouse models are widely utilized in neuro-research, as their evolutionary-conserved brain architecture serves as a miniaturized model that permits visualization of whole-tissue spatial relationships. However, translating the finding to human brain requires technologies that can resolve complex high-plex spatial biology at cellular and subcellular levels without compromising on data quality. Imaging Mass Cytometry™ (IMC™) technology enables quantitative spatial proteomic evaluation of the brain without the challenges of autofluorescence, tissue degradation and spectral overlap. This study seeks to demonstrate the value of IMC for bridging translational insights from mouse studies to human disease.Methods We used the Hyperion™ XTi Imaging System to simultaneously assess multiple individual protein markers across tissues with high dynamic range. We applied a 40-marker panel composed of the Maxpar™ OnDemand Mouse Immuno-Oncology IMC Panel Kit combined with the Maxpar Neuro Phenotyping IMC Panel Kit to evaluate the spatial biology of whole mouse GBM tissue. For human GBM, the Maxpar Neuro Phenotyping IMC Panel Kit formed the backbone of a 41-marker panel supplemented by the Human Immuno-Oncology IMC Panel. Subsequent pixel-clustering using MCD™ SmartViewer and single-cell analyses quantified expression patterns of structural and immune markers in GBM of both species.Results Conserved spatial features were detected in both human and mouse GBM samples, highlighting striking heterogeneity. Organized necrotic areas were surrounded by replicating Olig2-positive cells, indicating elevated tumor growth capabilities. A high degree of vascularization was observed in non-necrotic areas. A high concentration of lymphoid and myeloid immune cells was detected in tumor margins and in necrotic cores. Analysis identified distinct tumor regions: subsets of differentiated tumor cells, immune hot and cold zones, stromal compartments, de novo vascularization and extracellular matrix deposition (fig. 1 and 2). Such detailed spatial maps of the whole tissues are critical for locating expression signatures and tissue landmarks.Conclusions IMC establishes a critical bridge between preclinical models and human therapies. Cross-species validation accelerates marker discovery using mouse models as potential predictors of human tumor microenvironment (TME) development, stratifies immunotherapy candidate selection by utilizing high-throughput whole-tissue visualization and screening, and simultaneously explores multiple biological outputs to advance translational and clinical applications.For Research Use Only. Not for use in diagnostic procedures.Abstract 1224 Figure 1Whole slide Tissue Mode IMC image and pixel-clustering analysis of mouse GBM. Metabolically active tumor cells and activation of Ras signaling pathway were detected at the periphery of the tumor, and cell replication markers were observed in virtually all tumor cellsAbstract 1224 Figure 2Whole-sample pixel-clustering analysis of human GBM. The GBM sample demonstrated a dual stem-like origin and coexistence of pro-tumorigenic and anti-tumorigenic immune responses. The expression of shown markers suggests that the TME is conductive to immune evasion, which is a hallmark of aggressive GBM",
  "authors": [
    {
      "affiliations": [
        "Standard BioTools, Markham, ON, Canada"
      ],
      "name": "Nick Zabinyakov"
    },
    {
      "affiliations": [
        "Standard BioTools, Markham, ON, Canada"
      ],
      "name": "Thomas D Pfister"
    },
    {
      "affiliations": [
        "Standard BioTools, Markham, ON, Canada"
      ],
      "name": "David Howell"
    },
    {
      "affiliations": [
        "Standard BioTools, Markham, ON, Canada"
      ],
      "name": "Qanber Raza"
    },
    {
      "affiliations": [
        "Standard BioTools, Markham, ON, Canada"
      ],
      "name": "Liang Lim"
    },
    {
      "affiliations": [
        "Standard BioTools, South San Francisco, CA, USA"
      ],
      "name": "Christina Loh"
    }
  ],
  "title": "1224 Glioblastoma: bridging mouse model insights to human tumor microenvironment using imaging mass cytometry",
  "uid": "4e4eb44d-c99d-57c9-923b-a36b1ffbe716"
}