Distinct myeloid-derived suppressor cell populations in human glioblastoma

• 成果类型: Article
• 署名作者: Jackson, Christina; Cherry, Christopher; Bom, Sadhana; Dykema, Arbor G.; Wang, Rulin; Thompson, Elizabeth; Zhang, Ming; Li, Runzhe; Ji, Zhicheng; Hou, Wenpin; Zhan, Wentao; Zhang, Hao; Choi, John; Vaghasia, Ajay; Hansen, Landon; Wang, William; Bergsneider, Brandon; Jones, Kate M.; Rodriguez, Fausto; Weingart, Jon; Lucas, Calixto-Hope; Powell, Jonathan; Elisseeff, Jennifer; Yegnasubramanian, Srinivasan; Lim, Michael; Bettegowda, Chetan; Ji, Hongkai; Pardoll, Drew
• 署名单位: University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Johns Hopkins University; Stanford University; Johns Hopkins University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9750
• DOI: 10.1126/science.abm5214
• 发表日期: 2025-01-17
• 页码: 260-+
• 关键词: glioma stem-cells; immune cells; expression; roles; axis

摘要

The role of glioma-associated myeloid cells in tumor growth and immune evasion remains poorly understood. We performed single-cell RNA sequencing of immune and tumor cells from 33 gliomas, identifying two distinct myeloid-derived suppressor cell (MDSC) populations in isocitrate dehydrogenase-wild-type (IDT-WT) glioblastoma: an early progenitor MDSC (E-MDSC) population with up-regulation of metabolic and hypoxia pathways and a monocytic MDSC (M-MDSC) population. Spatial transcriptomics demonstrated that E-MDSCs geographically colocalize with metabolic stem-like tumor cells in the pseudopalisading region. Ligand-receptor analysis revealed cross-talk between these cells, where glioma stem-like cells produce chemokines attracting E-MDSCs, which in turn produce growth factors for the tumor cells. This interaction is absent in IDH-mutant gliomas, associated with hypermethylation and repressed gene expression of MDSC-attracting chemokines. Our study elucidates specific MDSCs that may facilitate glioblastoma progression and mediate tumor immunosuppression.