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Spatial single-cell profiling identifies protein kinase Cδ-expressing microglia with anti-tumor function in
Reza Mirzaei1, Reid McNeil2,3, Charlotte D'Mello4,5
1Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
Iscience
|January 8, 2026
Summary
Researchers discovered a specific type of microglia, called protein kinase Cδ (PKCδ)+ microglia, that can target and eliminate brain tumor-initiating cells (BTICs) in glioblastoma (GBM). Enhancing PKCδ levels boosts their anti-tumor activity.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- Glioblastoma (GBM) is characterized by complex interactions between diverse immune and tumor cell populations.
- The spatial organization of these cells significantly impacts disease progression.
- Understanding immune cell interactions with brain tumor-initiating cells (BTICs) is crucial for developing effective therapies.
Purpose of the Study:
- To map the immune landscape within the GBM microenvironment using integrated single-cell and spatial transcriptomics.
- To investigate the role of specific microglial subsets in interacting with BTICs.
- To identify potential therapeutic targets within the GBM immune microenvironment.
Main Methods:
- Integrated single-cell and spatial transcriptomic analysis of a GBM mouse model.
- Validation of findings in human GBM tissues.
- Functional assays to assess microglial cytotoxic and phagocytic capabilities.
- Analysis of patient datasets to correlate molecular markers with clinical outcomes.
Main Results:
- A distinct subset of microglia expressing protein kinase Cδ (PKCδ) was identified, localized near BTIC-rich regions.
- PKCδ expression in microglia was associated with enhanced inducible nitric oxide synthase (iNOS) expression, supporting cytotoxic and phagocytic functions.
- Increased PKCδ levels in microglia promoted the engulfment and killing of BTICs.
- Higher PKCδ expression in patient-derived GBM samples correlated with immune activation and cell death pathways.
Conclusions:
- PKCδ+ microglia represent a therapeutically relevant cell population within the GBM microenvironment.
- Targeting or enhancing PKCδ in microglia could be a promising strategy for GBM treatment.
- The study provides novel insights into the immune mechanisms underlying glioblastoma progression and potential therapeutic interventions.
