ArticleJournal for immunotherapy of cancer2019
Antisense oligonucleotide targeting CD39 improves anti-tumor T cell immunity.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 60 citations in OpenAlex.
- ATP is not always pro-inflammatory: rethinking purinergic signalling in cancer and autoimmunity.Purinergic signalling · 2026Review
- Targeting CD39 as a Therapeutic for Cancer Immunotherapy.Expert reviews in molecular medicine · 2026Review
- Cancer immunotherapy by adenosinergic CD39 and CD73 as emerging immune checkpoints.Discover oncology · 2025Review
- Advances in Hydrogel-Based Delivery of RNA Drugs for Antitumor Therapy.Gels (Basel, Switzerland) · 2025Review
- Nanoparticles for Cancer Immunotherapy: Innovations and Challenges.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Blocking the CD39/CD73 pathway synergizes with anti-CD20 bispecific antibody in nodal B-cell lymphoma.Journal for immunotherapy of cancer · 2025Article
- Advances and prospects of RNA delivery nanoplatforms for cancer therapy.Acta pharmaceutica Sinica. B · 2025Review
- Review
- "Find Me" and "Eat Me" signals: tools to drive phagocytic processes for modulating antitumor immunity.Cancer communications (London, England) · 2024Review
- [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
- The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Location of CD39Journal for immunotherapy of cancer · 2023Article
- Dual TLR9 and PD-L1 targeting unleashes dendritic cells to induce durable antitumor immunity.Journal for immunotherapy of cancer · 2023Article
- Post-transcriptional modification of mCell death & disease · 2023Article
- RNA Therapeutics for Improving CAR T-cell Safety and Efficacy.Cancer research · 2023Review
- Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy.Frontiers in immunology · 2023Review
- Adenosine A2a Receptor Antagonism Restores Additive Cytotoxicity by Cytotoxic T Cells in Metabolically Perturbed Tumors.Cancer immunology research · 2022Article
- Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?International journal of molecular sciences · 2022Review
- Review
- Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer cells are known to develop mechanisms to circumvent effective anti-tumor immunity. The two ectonucleotidases CD39 and CD73 are promising drug targets, as they act in concert to convert extracellular immune-stimulating ATP to adenosine. CD39 is expressed by different immune cell populations as well as cancer cells of different tumor types and supports the tumor in escaping immune recognition and destruction. Thus, increasing extracellular ATP and simultaneously reducing adenosine concentrations in the tumor can lead to effective anti-tumor immunity.
methodsWe designed locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) with specificity for human or mouse CD39 that do not need a transfection reagent or delivery system for efficient target knockdown. Knockdown efficacy of ASOs on mRNA and protein level was investigated in cancer cell lines and in primary human T cells. The effect of CD39 knockdown on ATP-degrading activity was evaluated by measuring levels of ATP in tumor cell supernatants and analysis of T cell proliferation in the presence of extracellular ATP. The in vivo effects of CD39-specific ASOs on target expression, anti-tumor immune responses and on tumor growth were analyzed in syngeneic mouse tumor models using multi-color flow cytometry.
resultsCD39-specific ASOs suppressed expression of CD39 mRNA and protein in different murine and human cancer cell lines and in primary human T cells. Degradation of extracellular ATP was strongly reduced by CD39-specific ASOs. Strikingly, CD39 knockdown by ASOs was associated with improved CD8
conclusionTargeting of CD39 by ASOs represents a promising state-of-the art therapeutic approach to improve immune responses against tumors.
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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.