Poon Candice C, Herbrich Shelley M, Chen Yulong, Hossain Anwar, Fuller Gregory N, Jindal Sonali, Basu Sreyashi, Ledbetter Daniel, Macaluso Marc, Phillips Lynnette M, Gumin Joy, He Zhong, Parker Kerrigan Brittany C, Singh Sanjay K, Singh Pratishtha, Zaman Mohammed Fayyad, Ng Tang Derek, Goswami Sangeeta, Lang Frederick F, Sharma Padmanee
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Clinical Neurosciences, The University of Calgary, Calgary, Canada.
Cancer Immunol Res. 2025 Jun 4;13(6):804-820. doi: 10.1158/2326-6066.CIR-24-0743.
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.
微血管增殖（MVP）是胶质母细胞瘤和其他世界卫生组织4级胶质瘤的疾病定义性特征。MVP在各种实体瘤中也是一个预后不良的标志物。尽管其具有临床意义，但MVP的机制和生物学后果仍存在争议且尚不清楚。在本研究中，我们对来自16例原发性胶质瘤患者样本（有和没有MVP）的配对CD45-CD105+血管/血管周基质细胞（PVSC）和CD45+CD105±免疫细胞进行了单细胞RNA测序。该分析揭示了在CD45-CD105+区室中存在与发育相关的间充质干细胞以及癌症相关成纤维细胞、周细胞、纤维肌细胞和平滑肌细胞。RNA速度分析确定PDGFRB为一个假定的驱动基因，在MVP背景下引导间充质干细胞向更成熟的PVSC分化。信号网络分析和数字空间分析揭示了PDGFRB+PVSC与血管周围微环境中富集的免疫抑制性髓细胞亚群之间的相互作用，提示了可靶向的受体-配体相互作用。此外，来自胶质瘤的MVP相关PVSC的基因特征在多种其他实体瘤中预测预后更差。本研究提供了胶质瘤中PVSC和免疫细胞的转录组细胞图谱，有助于完善传统上侧重于内皮细胞的MVP生物学模型。
