Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma.
IF: 17.694
Cited by: 17


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.

MeSH terms

Single-Cell Analysis
Spatial Analysis
Tumor Microenvironment


Coy, Shannon
Wang, Shu
Stopka, Sylwia A
Lin, Jia-Ren
Yapp, Clarence
Ritch, Cecily C
Salhi, Lisa
Baker, Gregory J
Rashid, Rumana
Baquer, Gerard
Regan, Michael
Khadka, Prasidda
Cole, Kristina A
Hwang, Jaeho
Wen, Patrick Y
Bandopadhayay, Pratiti
Santi, Mariarita
De Raedt, Thomas
Ligon, Keith L
Agar, Nathalie Y R
Sorger, Peter K
Touat, Mehdi
Santagata, Sandro