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

## TL;DR

This study identifies a specific type of brain immune cell, PKCδ+ microglia, that can fight glioblastoma tumors and suggests ways to enhance their anti-tumor activity.

## Contribution

The discovery of PKCδ+ microglia as anti-tumor cells in glioblastoma and their functional enhancement through PKCδ activation.

## Key findings

- PKCδ+ microglia are localized near tumor cells and show anti-tumor features.
- Increasing PKCδ levels improves microglial ability to kill tumor cells.
- Higher PKCδ expression in patients correlates with immune activation and cell death pathways.

## Abstract

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.

•Spatial heterogeneity shapes diverse cell interactions in the GBM microenvironment•Single-cell spatial profiling identifies anti-tumor PKCδ+ microglia in GBM•PKCδ activation boosts microglial phagocytosis and killing of BTICs•Increasing PKCδ reprograms microglia toward an anti-tumor phenotype

Spatial heterogeneity shapes diverse cell interactions in the GBM microenvironment

Single-cell spatial profiling identifies anti-tumor PKCδ+ microglia in GBM

PKCδ activation boosts microglial phagocytosis and killing of BTICs

Increasing PKCδ reprograms microglia toward an anti-tumor phenotype

Components of the immune system; Cancer; Transcriptomics; Model organism