ANGI-11. MESENCHYMAL STEM CELLS AND PERIVASCULAR STROMA ARE ASSOCIATED WITH MICROVASCULAR PROLIFERATION, IMMUNOSUPPRESSION, AND POOR OUTCOME IN GLIOMA

作者：Candice C. Poon, Shelley M. Herbrich, Yulong Chen, Anwar Hossain, Gregory N. Fuller, Sonali Jindal, Sreyashi Basu, Daniel Ledbetter, Marc Macaluso, Lynette M. Phillips, Joy Gumin, Zhong He, Brittany C. Parker Kerrigan, Sanjay K. Singh, Pratishtha Singh, Mohammed Fayyad Zamen, Derek Ng Tang, Sangeeta Goswami, Frederick F. Lang, Padmanee Sharma · 发表于：Neuro-Oncology · 年份：2025 · DOI：10.1093/neuonc/noaf201.0077 · 研究领域：Single-cell and spatial transcriptomics、Glioma Diagnosis and Treatment、Extracellular vesicles in disease

Abstract INTRODUCTION Microvascular proliferation (MVP) is a hallmark of glioblastoma (GBM) and other World Health Organization (WHO) grade 4 gliomas. MVP is also a poor prognostic marker in various solid tumors. Despite its clinical importance, the biological underpinnings of MVP are controversial and remain unclear, especially at the single cell level. METHODS In this study, we perform single cell RNA-sequencing (scRNA-seq) on paired CD45-CD105+ vascular/perivascular stromal cells (PVSCs) and CD45+CD105± immune cells from 16 primary glioma patient samples (7 glioblastomas, 4 astrocytomas, and 5 oligodendrogliomas for a total of 76,141 cells), both with and without MVP. scRNA-seq was complemented with spatial transcriptomic and multiplex immunofluorescence assays. RESULTS These analyses revealed the presence of developmentally-related mesenchymal stem cells (MSCs) alongside cancer-associated fibroblasts (CAFs), pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA velocity (trajectory) analysis identified PDGFRB as a putative driver gene guiding MSCs towards more mature PVSCs. Signaling network analyses 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 predicted worse prognosis in glioma and multiple other solid tumors. DISCUSSION T...