Mesenchymal Stem Cells and Fibroblasts Contribute to Microvascular Proliferation in Glioblastoma and are Correlated with Immunosuppression and Poor Outcome

Authors

Candice C Poon
Shelley M Herbrich
Yulong Chen
Anwar Hossain
Gregory N Fuller
Sonali Jindal
Sreyashi Basu
Daniel Ledbetter
Marc Macaluso
Lynnette M Phillips
Joy Gumin
Zhong He
Brittany C Parker Kerrigan
Sanjay K Singh
Pratishtha Singh
Mohammed Fayyad Zaman
Derek Ng Tang
Sangeeta Goswami
Frederick F Lang
Padmanee Sharma

Language

English

Publication Date

6-4-2025

Journal

Cancer Immunology Research

DOI

10.1158/2326-6066.CIR-24-0743

PMID

40131028

PMCID

PMC12175251

PubMedCentral® Posted Date

12-4-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Microvascular proliferation (MVP) is a disease-defining hallmark of glioblastoma and other World Health Organization grade 4 gliomas. MVP also serves as a poor prognostic marker in various solid tumors. Despite its clinical significance, the mechanisms and biological consequences of MVP are controversial and remain unclear. In this study, we performed single-cell RNA sequencing on paired CD45-CD105+ vascular/perivascular stromal cells (PVSC) and CD45+CD105± immune cells from 16 primary glioma patient samples, both with and without MVP. This analysis revealed the presence of developmentally related mesenchymal stem cells alongside cancer-associated fibroblasts, pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA velocity analysis identified PDGFRB as a putative driver gene guiding mesenchymal stem cells toward more mature PVSCs in the context of MVP. Signaling network analysis and digital spatial profiling uncovered interactions between PDGFRB+ PVSCs and immunosuppressive myeloid cell subsets enriched in the perivascular niche, suggesting targetable receptor-ligand interactions. Additionally, a gene signature of MVP-associated PVSCs from gliomas predicted worse prognosis in multiple other solid tumors. This study provides a transcriptomic cell atlas of PVSCs and immune cells in glioma, helping to refine the biological model of MVP which has traditionally focused on endothelial cells.

Keywords

Humans, Glioblastoma, Mesenchymal Stem Cells, Prognosis, Brain Neoplasms, Cell Proliferation, Female, Fibroblasts, Tumor Microenvironment, Receptor, Platelet-Derived Growth Factor beta, Microvessels, Male, Immune Tolerance

Published Open-Access

yes

Recommended Citation

Poon, Candice C; Herbrich, Shelley M; Chen, Yulong; et al., "Mesenchymal Stem Cells and Fibroblasts Contribute to Microvascular Proliferation in Glioblastoma and are Correlated with Immunosuppression and Poor Outcome" (2025). Faculty, Staff and Student Publications. 5652.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5652