ArticleJournal for immunotherapy of cancer2020
Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 116 citations in OpenAlex.
- Continuous replenishment of the dysfunctional CD8 T cell axis is associated with response to chemoimmunotherapy in advanced breast cancer.Cell reports. Medicine · 2025Trial
- Construction of an ATP hydrolysis-related 11-gene signature for predicting prognosis and immune response in hepatocellular carcinoma.Medicine · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment.Cell biochemistry and function · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Emerging chemical strategies for CD38 inhibition: restoring NADBioorganic & medicinal chemistry · 2026Review
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- Nucleotide-Derived Competitive Inhibitors of Ectonucleotidase CD39─A Promising Extracellular Target for Immunotherapy of Cancer.Journal of medicinal chemistry · 2026Article
- Stem Cells and their Key Derivatives in Degenerative Musculoskeletal Diseases.Stem cell reviews and reports · 2026Review
- What Is-and What Is Not-Immunogenic Cell Death? Functional Definitions, Experimental Standards, and Common Pitfalls.International journal of molecular sciences · 2026Review
- The mechanisms of regulatory T cells in the immune microenvironment of multiple myeloma and clinical significance.Frontiers in immunology · 2026Review
- Hypoxia-driven tumor immune escape: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- The tumor microenvironment in leukemia: molecular pathways of immune evasion.Frontiers in immunology · 2026Review
- Cancer immunotherapy by adenosinergic CD39 and CD73 as emerging immune checkpoints.Discover oncology · 2025Review
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
- Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies.Signal transduction and targeted therapy · 2025Review
- P2 purinergic receptors regulate the progression of colorectal cancer.Purinergic signalling · 2025Review
- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPD1/PDL1-directed therapies have been unsuccessful for multiple myeloma (MM), an incurable cancer of plasma cells in the bone marrow (BM). Therefore, other immune checkpoints such as extracellular adenosine and its immunosuppressive receptor should be considered. CD39 and CD73 convert extracellular ATP to adenosine, which inhibits T-cell effector functions via the adenosine receptor A2A (A2AR). We set out to investigate whether blocking the adenosine pathway could be a therapy for MM.
methodsExpression of CD39 and CD73 on BM cells from patients and T-cell proliferation were determined by flow cytometry and adenosine production by Liquid chromatograpy-mass spectrometry (HPCL/MS). ENTPD1 (CD39) mRNA expression was determined on myeloma cells from patients enrolled in the publicly available CoMMpass study. Transplantable 5T33MM myeloma cells were used to determine the effect of inhibiting CD39, CD73 and A2AR in mice in vivo.
resultsElevated level of adenosine was found in BM plasma of MM patients. Myeloma cells from patients expressed CD39, and high gene expression indicated reduced survival. CD73 was found on leukocytes and stromal cells in the BM. A CD39 inhibitor, POM-1, and an anti-CD73 antibody inhibited adenosine production and reduced T-cell suppression in vitro in coculture of myeloma and stromal cells. Blocking the adenosine pathway in vivo with a combination of Sodium polyoxotungstate (POM-1), anti-CD73, and the A2AR antagonist AZD4635 activated immune cells, increased interferon gamma production, and reduced the tumor load in a murine model of MM.
conclusionsOur data suggest that the adenosine pathway can be successfully targeted in MM and blocking this pathway could be an alternative to PD1/PDL1 inhibition for MM and other hematological cancers. Inhibitors of the adenosine pathway are available. Some are in clinical trials and they could thus reach MM patients fairly rapidly.
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