ArticleCancer discovery2019
Targeting CD39 in Cancer Reveals an Extracellular ATP- and Inflammasome-Driven Tumor Immunity.
Article in Cancer discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
173 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.
- High-dimensional analysis of the adenosine pathway in high-grade serous ovarian cancer.Journal for immunotherapy of cancer · 2021Pooled it
- Spatial proteomics deciphers the immune niche landscape of non-ampullary duodenal adenocarcinoma.British journal of cancer · 2026Article
- CD39 on CD8European journal of immunology · 2026Review
- Augmenting CAR T cell functionality and metabolism through CD39 downtuning.Molecular therapy. Oncology · 2026Article
- CD73 disruption with tumor-specific CRISPR/Cas9 nanoparticles reduces adenosine-mediated immunosuppression and amplifies response to chemotherapy.Nature communications · 2026Article
- Reprogramming the immune suppressive tumor microenvironment in glioma enhances the efficacy of immune-mediated gene therapy.Molecular therapy. Oncology · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- The Mechanism of NLRP3 Inflammasome Activation and Its Roles in Chronic Rhinosinusitis.World journal of otorhinolaryngology - head and neck surgery · 2026Review
- The P2X4-P2X7 purinergic axis in alcohol-related liver disease: from fibrogenesis to immunotherapy resistance.Purinergic signalling · 2026Review
- Deficiency of lysosomal TMEM175 in myeloid macrophages exerts anti-tumor immunity via inflammasome and cross-presentation pathway.Nature communications · 2026Article
- Targeting CD39 as a Therapeutic for Cancer Immunotherapy.Expert reviews in molecular medicine · 2026Review
- Recent Advances in Smart Stimulus-Responsive Hydrogels for Precision Drug Delivery in Tumours.Gels (Basel, Switzerland) · 2026Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
- Caffeine-mediated CD39Frontiers in immunology · 2026Article
- Targeting CD39 in combination with IL-2/anti-IL-2 complexes enhances cytotoxic immunity and limits tumor progression.Frontiers in immunology · 2026Article
- Metabolic reprogramming networks in the gastric cancer tumor microenvironment: an integrated axis of nutrient competition, metabolic crosstalk, and immunosuppression.Frontiers in immunology · 2026Review
- Pannexin-1-mediated ATP signaling as a driver of immune communication and chronic inflammation in HIV infection.Frontiers in immunology · 2026Review
- T cell exhaustion in poorly immunogenic HCC is partially rescued by checkpoint blockade but suppressed by oncolytic virotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Cancer immunotherapy by adenosinergic CD39 and CD73 as emerging immune checkpoints.Discover oncology · 2025Review
- Increased CD103Cancer immunology, immunotherapy : CII · 2025Article
113 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
30 authors at 5 institutions in 3 countries.
Funding
Abstract
We explored the mechanism of action of CD39 antibodies that inhibit ectoenzyme CD39 conversion of extracellular ATP (eATP) to AMP and thus potentially augment eATP-P2-mediated proinflammatory responses. Using syngeneic and humanized tumor models, we contrast the potency and mechanism of anti-CD39 mAbs with other agents targeting the adenosinergic pathway. We demonstrate the critical importance of an eATP-P2X7-ASC-NALP3-inflammasome-IL18 pathway in the antitumor activity mediated by CD39 enzyme blockade, rather than simply reducing adenosine as mechanism of action. Efficacy of anti-CD39 activity was underpinned by CD39 and P2X7 coexpression on intratumor myeloid subsets, an early signature of macrophage depletion, and active IL18 release that facilitated the significant expansion of intratumor effector T cells. More importantly, anti-CD39 facilitated infiltration into T cell-poor tumors and rescued anti-PD-1 resistance. Anti-human CD39 enhanced human T-cell proliferation and Th1 cytokine production and suppressed human B-cell lymphoma in the context of autologous Epstein-Barr virus-specific T-cell transfer. SIGNIFICANCE: Overall, these data describe a potent and novel mechanism of action of antibodies that block mouse or human CD39, triggering an eATP-P2X7-inflammasome-IL18 axis that reduces intratumor macrophage number, enhances intratumor T-cell effector function, overcomes anti-PD-1 resistance, and potentially enhances the efficacy of adoptive T-cell transfer.
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Registered trials
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.