ArticleOncoimmunology2016
The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- High-dimensional analysis of the adenosine pathway in high-grade serous ovarian cancer.Journal for immunotherapy of cancer · 2021Pooled it
- Targeting CD39 as a Therapeutic for Cancer Immunotherapy.Expert reviews in molecular medicine · 2026Review
- IL27 expression and IL27RA-dependent cellular responses are associated with biochemical recurrence and immune-regulatory features in prostate cancer.Frontiers in immunology · 2026Article
- Purinergic signaling modulates endothelial-to-mesenchymal transition in human aortic valve endothelial cells.BBA advances · 2026Article
- Expression of TIM-3 and Gal-9 Immune Checkpoints in Chronic Lymphocytic Leukemia: The Potential Role of Interleukin-27.Current issues in molecular biology · 2025Article
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Harnessing IL-27: challenges and potential in cancer immunotherapy.Clinical and experimental medicine · 2025Review
- Metabolic instruction of the graft-versus-leukemia immunity.Frontiers in immunology · 2024Review
- Review immune response of targeting CD39 in cancer.Biomarker research · 2023Review
- CD39/CD73/A2AR pathway and cancer immunotherapy.Molecular cancer · 2023Review
- Sterile inflammation in liver transplantation.Frontiers in medicine · 2023Review
- Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy.Frontiers in immunology · 2023Review
- Chemobrain: An accelerated aging process linking adenosine AInternational review of neurobiology · 2023Review
- TIGIT signaling and its influence on T cell metabolism and immune cell function in the tumor microenvironment.Frontiers in oncology · 2023Review
- Nucleoside transporters and immunosuppressive adenosine signaling in the tumor microenvironment: Potential therapeutic opportunities.Pharmacology & therapeutics · 2022Review
- Targeting purine metabolism in ovarian cancer.Journal of ovarian research · 2022Review
- Glycoengineered anti-CD39 promotes anticancer responses by depleting suppressive cells and inhibiting angiogenesis in tumor models.The Journal of clinical investigation · 2022Article
- PD-L1iScience · 2022Article
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Frontiers in oncology · 2022Review
- ATP and cancer immunosurveillance.The EMBO journal · 2021Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14(+) CD163(+) TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14(high) CD163(high) CD39(high) macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163(+) macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages.
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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.