Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma - Sorbonne Université Access content directly
Journal Articles Nature Communications Year : 2022

Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma

Clarence Yapp
Cecily C Ritch
Lisa Salhi
Gregory J Baker
Gerard Baquer
Nathalie y R Agar
Peter K Sorger
Sandro Santagata

Abstract

Abstract How the glioma immune microenvironment fosters tumorigenesis remains incompletely defined. Here, we use single-cell RNA-sequencing and multiplexed tissue-imaging to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioma. We show that microglia are the predominant source of CD39, while tumor cells principally express CD73. In glioblastoma, CD73 is associated with EGFR amplification, astrocyte-like differentiation, and increased adenosine, and is linked to hypoxia. Glioblastomas enriched for CD73 exhibit inflammatory microenvironments, suggesting that purinergic signaling regulates immune adaptation. Spatially-resolved single-cell analyses demonstrate a strong spatial correlation between tumor-CD73 and microglial-CD39, with proximity associated with poor outcomes. Similar spatial organization is present in pediatric high-grade gliomas including H3K27M-mutant diffuse midline glioma. These data reveal that purinergic signaling in gliomas is shaped by genotype, lineage, and functional state, and that core enzymes expressed by tumor and myeloid cells are organized to promote adenosine-rich microenvironments potentially amenable to therapeutic targeting.
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hal-04534814 , version 1 (05-04-2024)

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Shannon Coy, Shu Wang, Sylwia A Stopka, Jia-Ren Lin, Clarence Yapp, et al.. Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma. Nature Communications, 2022, 13, pp.4814. ⟨10.1038/s41467-022-32430-w⟩. ⟨hal-04534814⟩
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