Pericytes change function depending on glioblastoma vicinity: emphasis on immune regulation.

Abstract

Glioblastoma (GBM), the most aggressive brain tumor in adults, is characterized by its infiltrative growth along the perivascular space. Mural cells (MCs), encompassing pericytes and smooth muscle cells, are multifunctional perivascular cells implicated in GBM progression. MCs not only facilitate vascular co-option but have also been suggested to contribute to the immunosuppressive tumor microenvironment, promoting tumor growth and migration. However, whether MC interactions with immune cells differ based on their proximity to the tumor remains unclear. Using single-cell RNA sequencing, we analyzed MC transcriptome profiles across distinct regions relative to the tumor mass in mouse and human GBM samples. Tumor-residing MCs exhibited profound phenotypic changes, showing upregulated gene expression and enhanced signaling activity toward immune cells, with region-specific ligand-receptor interactions. Conversely, border-residing MCs, despite their abundance, showed reduced activation and lacked distinct transcriptional profiles. These findings reveal spatially defined transcriptional heterogeneity in MCs within the GBM microenvironment, underscoring their dynamic role in the GBM microenvironment. This study provides novel insights into MC responses in GBM, identifying potential avenues for targeting MC-immune-cell interactions in therapeutic interventions.