ArticleThe Journal of clinical investigation2022
Glycoengineered anti-CD39 promotes anticancer responses by depleting suppressive cells and inhibiting angiogenesis in tumor models.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- A STING signaling relay from tumor cells to macrophages mediates the improved efficacy of combination chemotherapy in pancreatic cancer.Journal of biomedical science · 2026Article
- Causal Inference and Prognostic Modeling in Colorectal Cancer through Integration of Computational Pathology and Mendelian Randomization.Annals of surgical oncology · 2026Article
- Targeting CD39 as a Therapeutic for Cancer Immunotherapy.Expert reviews in molecular medicine · 2026Review
- The purinergic signaling interfaces in breast cancer angiogenesis.Purinergic signalling · 2026Review
- Targeting CD39 in combination with IL-2/anti-IL-2 complexes enhances cytotoxic immunity and limits tumor progression.Frontiers in immunology · 2026Article
- The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy.Frontiers in immunology · 2026Review
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Targeting Myeloid Cells for Cancer Immunotherapy.Cancer immunology research · 2025Review
- Extracellular Adenosine in Gastric Cancer: The Role of GCSCs.International journal of molecular sciences · 2025Article
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
- Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Impact of Estrogen on Purinergic Signaling in Microvascular Disease.International journal of molecular sciences · 2025Review
- Cd39 and P2rx7-Wnt signaling enhance blast pathogenicity in an experimental model of acute myeloid leukemia.Haematologica · 2025Article
- Myeloid-derived suppressor cells in cancer and cancer therapy.Nature reviews. Clinical oncology · 2024Review
- Development of a CD39 nanobody and its enhancement to chimeric antigen receptor T cells efficacy against ovarian cancer in preclinical studies.Theranostics · 2024Article
- The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Therapeutic targeting of tumour myeloid cells.Nature reviews. Cancer · 2023Review
- Beyond antibody fucosylation: α-(1,6)-fucosyltransferase (Fut8) as a potential new therapeutic target for cancer immunotherapy.Antibody therapeutics · 2023Review
- CD39/CD73/A2AR pathway and cancer immunotherapy.Molecular cancer · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Immunosuppressive cells accumulating in the tumor microenvironment constitute a formidable barrier that interferes with current immunotherapeutic approaches. A unifying feature of these tumor-associated immune and vascular endothelial cells appears to be the elevated expression of ectonucleotidase CD39, which in tandem with ecto-5'-nucleotidase CD73, catalyzes the conversion of extracellular ATP into adenosine. We glycoengineered an afucosylated anti-CD39 IgG2c and tested this reagent in mouse melanoma and colorectal tumor models. We identified major biological effects of this approach on cancer growth, associated with depletion of immunosuppressive cells, mediated through enhanced Fcγ receptor-directed (FcγR-directed), antibody-dependent cellular cytotoxicity (ADCC). Furthermore, regulatory/exhausted T cells lost CD39 expression, as a consequence of antibody-mediated trogocytosis. Most strikingly, tumor-associated macrophages and endothelial cells with high CD39 expression were effectively depleted following antibody treatment, thereby blocking angiogenesis. Tumor site-specific cellular modulation and lack of angiogenesis synergized with chemotherapy and anti-PD-L1 immunotherapy in experimental tumor models. We conclude that depleting suppressive cells and targeting tumor vasculature, through administration of afucosylated anti-CD39 antibody and the activation of ADCC, comprises an improved, purinergic system-modulating strategy for cancer therapy.
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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.