Spatial single-cell profiling identifies protein kinase Cδ-expressing microglia with anti-tumor function in glioblastoma.

Glioblastoma (GBM) contains diverse immune and tumor cell populations whose spatial organization influences disease progression. To better understand how immune cells interact with brain tumor-initiating cells (BTICs), we applied integrated single-cell and spatial transcriptomic approaches to map the immune landscape in a GBM mouse model. This analysis revealed a distinct subset of microglia expressing protein kinase Cδ (PKCδ) that localizes near BTIC-rich regions and displays features associated with anti-tumor activity. We validated the presence of PKCδ(+) microglia in human GBM tissues and found that PKCδ enhances inducible nitric oxide synthase (iNOS) expression, supporting microglial cytotoxic and phagocytic functions. Increasing PKCδ levels in microglia, either through adeno-associated viral delivery or niacin treatment, strengthened their ability to engulf and kill BTICs. Analysis of patient datasets further showed that higher PKCδ expression associates with immune activation and cell death pathways. These findings identify PKCδ(+) microglia as a therapeutically relevant component of the GBM microenvironment.