ArticleCancer immunology, immunotherapy : CII2011
Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity.
Article in Cancer immunology, immunotherapy : CII, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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115 citing papers in PubMed, 184 citations in OpenAlex.
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- Enhanced CD33 CAR-NK cells secreting anti-CD73scFv overcome adenosine-mediated immunosuppression and improve anti-AML efficacy.Journal for immunotherapy of cancer · 2026Article
- Emerging role of microRNAs as modulators of the tumor immune microenvironment.Journal for immunotherapy of cancer · 2026Review
- Immune Evasion in Ovarian Cancer Peritoneal Metastasis: Mechanisms and Biomarker-Guided Therapeutic Matching.Journal of cellular physiology · 2026Review
- The expression of CD39 on NK cells relates to poor HIV-1 suppression in treatment-naïve HIV-1-infected individuals: Association with elevated IL-10 secretion and TIGIT co-expression.Virologica Sinica · 2026Article
- Caffeine-mediated CD39Frontiers in immunology · 2026Article
- Purinergic Signaling in Ovarian Carcinoma.Advanced pharmaceutical bulletin · 2025Review
- Tumor Microenvironment: Recent Advances in Immunotherapies of Pancreatic Cancer.Medicina (Kaunas, Lithuania) · 2025Review
- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- Enzymatic and microenvironmental regulation in adenosine metabolism-mediated immunosuppression.Frontiers in immunology · 2025Review
- Identification of SIN3A as a Promising Epigenetic Target Against Allergic Rhinitis.Journal of inflammation research · 2025Article
- Integrative transcriptomics and single-cell transcriptomics analyses reveal potential biomarkers and mechanisms of action in papillary thyroid carcinoma.Frontiers in genetics · 2025Article
- "Find Me" and "Eat Me" signals: tools to drive phagocytic processes for modulating antitumor immunity.Cancer communications (London, England) · 2024Review
- The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies.Acta pharmaceutica Sinica. B · 2024Review
- Systemic Delivery of Paclitaxel by Find-Me Nanoparticles Activates Antitumor Immunity and Eliminates Tumors.ACS nano · 2024Article
- Regulatory role of CD39 and CD73 in tumor immunity.Future oncology (London, England) · 2024Review
- Metabolic instruction of the graft-versus-leukemia immunity.Frontiers in immunology · 2024Review
- CD39American journal of cancer research · 2024Article
- [ARL67156, a small-molecule CD39 inhibitor, enhances natural killer cell cytotoxicity against gastric cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
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Abstract
The ectonucleotidases CD39 and CD73 degrade immune stimulatory ATP to adenosine that inhibits T and NK cell responses via the A(2A) adenosine receptor (ADORA2A). This mechanism is used by regulatory T cells (T(reg)) that are associated with increased mortality in OvCA. Immunohistochemical staining of human OvCA tissue specimens revealed further aberrant expression of CD39 in 29/36 OvCA samples, whereas only 1/9 benign ovaries showed weak stromal CD39 expression. CD73 could be detected on 31/34 OvCA samples. While 8/9 benign ovaries also showed CD73 immunoreactivity, expression levels were lower than in tumour specimens. Infiltration by CD4(+) and CD8(+) T cells was enhanced in tumour specimens and significantly correlated with CD39 and CD73 levels on stromal, but not on tumour cells. In vitro, human OvCA cell lines SK-OV-3 and OaW42 as well as 11/15 ascites-derived primary OvCA cell cultures expressed both functional CD39 and CD73 leading to more efficient depletion of extracellular ATP and enhanced generation of adenosine as compared to activated T(reg). Functional assays using siRNAs against CD39 and CD73 or pharmacological inhibitors of CD39, CD73 and ADORA2A revealed that tumour-derived adenosine inhibits the proliferation of allogeneic human CD4(+) T cells in co-culture with OvCA cells as well as cytotoxic T cell priming and NK cell cytotoxicity against SK-OV3 or OAW42 cells. Thus, both the ectonucleotidases CD39 and CD73 and ADORA2A appear as possible targets for novel treatments in OvCA, which may not only affect the function of T(reg) but also relieve intrinsic immunosuppressive properties of tumour and stromal cells.
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