ArticleNeuro-oncology2013
Synergy between the ectoenzymes CD39 and CD73 contributes to adenosinergic immunosuppression in human malignant gliomas.
Article in Neuro-oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- T cell immunity in glioma and potential implications for immunotherapy: A systematic review.Neuro-oncology · 2026Pooled it
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- Article
- The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.Frontiers in cell and developmental biology · 2026Review
- CD73 inhibitor AB680 suppresses glioblastoma in mice by inhibiting purine metabolism and promoting P2RY12Acta pharmacologica Sinica · 2025Article
- Immune checkpoints in immune response to glioma: two sides of the same coin.Frontiers in immunology · 2025Review
- Neuro-immune-tumor axis in gliomas: a review of mechanisms, models, and translational opportunities.Frontiers in immunology · 2025Review
- Development of a hydrogel-based three-dimensional (3D) glioblastoma cell lines culture as a model system for CD73 inhibitor response study.Biomedical engineering online · 2024Article
- Mitochondria-related HSDL2 is a potential biomarker in temporal lobe epilepsy by modulating astrocytic lipid metabolism.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- An Update on the Clinical Status, Challenges, and Future Directions of Oncolytic Virotherapy for Malignant Gliomas.Current treatment options in oncology · 2024Review
- ENTPD1 (CD39) and NT5E (CD73) expression in human glioblastoma: an in silico analysis.Purinergic signalling · 2024Article
- Characterization of purinergic signaling in tumor-infiltrating lymphocytes from lower- and high-grade gliomas.Purinergic signalling · 2024Article
- Treatment advances in high-grade gliomas.Frontiers in oncology · 2024Review
- Tumor Microenvironment Responsive CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- AInternational journal of molecular sciences · 2023Article
- EGFR alterations in glioblastoma play a role in antitumor immunity regulation.Frontiers in oncology · 2023Review
- Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma.Nature communications · 2022Article
- Review
- MTAP loss correlates with an immunosuppressive profile in GBM and its substrate MTA stimulates alternative macrophage polarization.Scientific reports · 2022Article
- Is the regulation by miRNAs of NTPDase1 and ecto-5'-nucleotidase genes involved with the different profiles of breast cancer subtypes?Purinergic signalling · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe importance of ectoenzymes CD39 and CD73 in mediating adenosinergic immunosuppression has been recognized, but their roles in human malignant glioma-associated immunosuppression remain largely unknown.
methodsIn this study, the ectoenzyme characteristics of malignant glioma cells and infiltrating CD4(+) T lymphocytes isolated from newly diagnosed malignant glioma patients were investigated. The ectoenzyme activities of both cell populations were determined by nucleotide hydrolysis assay. The immunosuppressive property of the CD39-CD73 synergic effect was evaluated via responder T-cell proliferation assay.
resultsWe observed that CD39(-)CD73(+) glioma cells and infiltrating CD4(+)CD39(high)CD73(low) T lymphocytes exhibited 2 distinct but complementary ectoenzyme phenotypes, which were further verified by enzyme activity assay. The nucleotide hydrolysis cascade was incomplete unless CD39 derived from T lymphocytes and CD73 collaborated synergistically. We demonstrated that increased suppression of responder CD4(+) T-cell proliferation suppression was induced by CD4(+)CD39(+) T cells in the presence of CD73(+) glioma cells, which could be alleviated by the CD39 inhibitor ARL67156, the CD73 inhibitor APCP, or the adenosine receptor A2aR antagonist SCH58261. In addition, survival analysis suggested that CD73 downregulation was a positive prognostic factor related to the extended disease-free survival of glioblastoma patients.
conclusionsOur data indicate that glioma-derived CD73 contributes to local adenosine-mediated immunosuppression in synergy with CD39 from infiltrating CD4(+)CD39(+) T lymphocytes, which could become a potential therapeutic target for treatment of malignant glioma and other immunosuppressive diseases.
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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.