据介绍，胶质瘤相关髓系细胞在肿瘤生长和免疫逃逸中的作用仍未完全明晰。
研究人员对33例胶质瘤的免疫细胞和肿瘤细胞，进行了单细胞RN 测序，在异柠檬酸脱氢酶野生型（IDH-WT）胶质母细胞瘤中，识别出两种不同的髓系来源抑制细胞（MDSC）群体：一个是早期祖细胞样MDSC（E-MDSC）群体，其代谢和缺氧相关通路呈上调状态；另一个是单核细胞样MDSC（M-MDSC）群体。
空间转录组学显示，E-MDSC在空间上与假栅栏状区，具有代谢特征的肿瘤干细胞样细胞共定位。配体-受体分析揭示了这些细胞之间存在相互作用，即胶质瘤干细胞样细胞产生趋化因子吸引E-MDSC，而E-MDSC反过来为肿瘤细胞产生生长因子。这种相互作用在IDH突变型胶质瘤中不存在，这与吸引MDSC的趋化因子发生高甲基化，及基因表达受抑制有关。
总之，这一研阐明了可能促进胶质母细胞瘤进展，并介导肿瘤免疫抑制的特定MDSC群体。
附：英文原文
Title: Distinct myeloid-derived suppressor cell populations in human glioblastoma
Author: Christina Jackson, Christopher Cherry, Sadhana Bom, Arbor G. Dykema, Rulin Wang, Elizabeth Thompson, Ming Zhang, Runzhe Li, Zhicheng Ji, Wenpin Hou, Wentao Zhan, Hao Zhang, John Choi, Ajay Vaghasia, Landon Hansen, William Wang, Brandon Bergsneider, Kate M. Jones, Fausto Rodriguez, Jon Weingart, Calixto-Hope Lucas, Jonathan Powell, Jennifer Elisseeff, Srinivasan Yegnasubramanian, Michael Lim, Chetan Bettegowda, Hongkai Ji, Drew Pardoll
Issue&Volume: 2025-01-17
Abstract: 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.
DOI: abm5214
Source: https://www.science.org/doi/10.1126/science.abm5214