Evidence map›Paper›PMID 35973991›Full record

ArticleNature communications2022

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

Shannon Coy, Shu Wang, Sylwia A Stopka, Jia-Ren Lin, Clarence Yapp, Cecily C Ritch, Lisa Salhi, Gregory J Baker, Rumana Rashid, Gerard Baquer and 13 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
10.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 77 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Targeting CD39 as a Therapeutic for Cancer Immunotherapy.Expert reviews in molecular medicine · 2026
    Review
  14. Article
  15. Review
  16. Review
  17. SEAL: Spatially-resolved Embedding Analysis with Linked Imaging Data.IEEE transactions on visualization and computer graphics · 2026
    Article
  18. Review
  19. Review
  20. Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 5 institutions in 2 countries.

Shannon CoyDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Shu WangLaboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Boston, MA, USA.
Sylwia A StopkaDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jia-Ren LinLaboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Boston, MA, USA.
Clarence YappLaboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Boston, MA, USA.ORCID 0000-0003-1144-5710
Cecily C RitchDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7651-0419
Lisa SalhiSorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Epinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.ORCID 0000-0003-4654-9552
Gregory J BakerLaboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Boston, MA, USA.ORCID 0000-0002-5196-3961
Rumana RashidDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gerard BaquerDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4433-4972
Michael ReganDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Prasidda KhadkaDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID 0000-0002-3732-7600
Kristina A ColeChildren's Hospital of Philadelphia, University of Pennsylvania, Pennsylvania, PA, USA.
Jaeho HwangDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Patrick Y WenDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Pratiti BandopadhayayDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID 0000-0002-4175-4760
Mariarita SantiDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Thomas De RaedtChildren's Hospital of Philadelphia, University of Pennsylvania, Pennsylvania, PA, USA.
Keith L LigonDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7733-600X
Nathalie Y R AgarDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3149-3146
Peter K SorgerLaboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Boston, MA, USA.ORCID 0000-0002-3364-1838
Mehdi TouatSorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Epinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France. mehdi.touat@aphp.fr.ORCID 0000-0002-5910-7799
Sandro SantagataDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ssantagata@bics.bwh.harvard.edu.ORCID 0000-0002-7528-9668
Brigham and Women's Hospital · USHarvard University · USChildren's Hospital of Philadelphia · USBroad Institute · USCentre National de la Recherche Scientifique · FR

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI KEITH LLOYD LIGON · 2013 to 2026
$26.0M
TRAINING PROGRAM FOR MD/PHD STUDENTST32GM008208 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STEINMAN, RICHARD A · 1987 to 2021
$15.4M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
National Metabolomics Data Repository - nextgen Metabolomics WorkbenchU2CDK119886 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2018 to 2021
$12.7M
TRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8M
TRD 3 - Enabling Technologies for Intraprocedural GuidanceP41EB028741 · NIBIB · BRIGHAM AND WOMEN'S HOSPITAL · PI Nobuhiko Hata, CLARE M TEMPANY · 2021 to 2026
$10.7M
MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
Trans Network ProjectU54CA210180 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SARKARIA, JANN N., WHITE, FOREST M · 2016 to 2020
$10.2M
Characterizing TP53 and PPM1D mutations as resistance drivers to radiation therapy in Diffuse Intrinsic Pontine GliomasR01CA219943 · NCI · BROAD INSTITUTE, INC. · PI BEROUKHIM, RAMEEN, LIGON, KEITH LLOYD · 2017 to 2021
$2.5M
Investigating the HSF1 Cancer NetworkR01CA194005 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI SANTAGATA, SANDRO · 2016 to 2020
$2.0M
NCI NIH HHS P01 CA163205NCI NIH HHS P30 CA006516NCI NIH HHS R01 CA194005NCI NIH HHS R01 CA219943NCI NIH HHS T32 CA009216NCI NIH HHS U54 CA210180NCI NIH HHS U54 CA225088NIBIB NIH HHS P41 EB028741NIBIB NIH HHS T32 EB025823NIDDK NIH HHS U2C DK119886NIGMS NIH HHS T32 GM007748NIGMS NIH HHS T32 GM008208NIGMS NIH HHS T32 GM008313
6 · The paper itself

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.

Indexed as

GlioblastomaGlioma5'-NucleotidaseAdenosineChildHumansSingle-Cell AnalysisSpatial AnalysisTumor Microenvironment5'-NucleotidaseAdenosine

Identifiers

PMID35973991
PMCPMC9381513
OpenAlexW4292183618

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.