ArticleCancer immunology research2023
CD73 Inhibits cGAS-STING and Cooperates with CD39 to Promote Pancreatic Cancer.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 70 citations in OpenAlex.
- A Phase Ib/II Randomized Clinical Trial of Oleclumab with or without Durvalumab plus Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- PARP7 inhibitors enhance the immunogenic effects of radiation in pancreatic cancer cells.Molecular therapy. Oncology · 2026Article
- cGAS-STING pathway activation drives the cold-to-hot tumor transition and sensitizes immunotherapy.Cancer biology & medicine · 2026Review
- EBV hijacks the metabolic function of CD73 to resist the antitumor function of NK cells.NPJ precision oncology · 2026Article
- ADA2-Functionalized OMVs Remodel the Tumor Microenvironment in Pancreatic Cancer.Pharmaceutics · 2026Article
- Regulatory B-cell states in NSCLC immunotherapy resistance: mechanisms, spatial context and translational implications.Cancer immunology, immunotherapy : CII · 2026Review
- Engineering an AIEgen-based platform integrating CRISPR/Cas9 to remodel the tumor microenvironment and reinforce photo-immunotherapy against glioblastom.Signal transduction and targeted therapy · 2026Article
- Dietary Fat Content Influences PanIN Progression and Pancreatic Cancer Development in Mice.Cancer research communications · 2026Article
- Nanomedicine leverages cuproptosis-mediated cGAS-STING activation to enhance antitumor immunity.Journal of nanobiotechnology · 2026Review
- CD73 blockade alleviates collagen-induced arthritis by inhibiting synovial fibroblast activity.Iranian journal of basic medical sciences · 2026Article
- TAM-targeted nanomedicine in cancer: biological basis, therapeutic strategies, and translational perspectives.Theranostics · 2026Review
- The cGAS-STING pathway in tumor immunity: dual roles, regulatory mechanisms, and precision therapeutic strategies.Frontiers in pharmacology · 2026Review
- cGAS-STING and PANoptosis: Interplay, Underlying Mechanisms, and Therapeutic Targets.Drug design, development and therapy · 2026Review
- Overcoming multidimensional immunotherapy resistance in PDAC: from microenvironment to clinic.Frontiers in immunology · 2026Review
- Overcoming EGFR-Mediated Dendritic Cell Dysfunction to Enhance Anti-tumor Immunity in EGFR-Mutant NSCLC by Precisely Targeting CD73 With pH-responsive Nanocarriers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- CD39+CD8+ T cell infiltration is associated with clinical outcomes of subsequent immunotherapy in advanced EGFR-mutant non-small cell lung cancer.Therapeutic advances in medical oncology · 2026Article
- Dietary Fat Content Influences PanIN Progression and Pancreatic Cancer Development in Mice.bioRxiv : the preprint server for biology · 2025Article
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
- CD73 inhibitor AB680 suppresses glioblastoma in mice by inhibiting purine metabolism and promoting P2RY12Acta pharmacologica Sinica · 2025Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells. In mouse transplanted KPC tumors, both CD39 and CD73 on myeloid cells, as well as CD73 on tumor cells, promoted polarization of infiltrating myeloid cells towards an M2-like phenotype, which enhanced tumor growth. CD39 on tumor-specific CD8+ T cells and pancreatic stellate cells also suppressed IFNγ production by T cells. Although therapeutic inhibition of CD39 or CD73 alone significantly delayed tumor growth in vivo, targeting of both ectonucleotidases exhibited markedly superior antitumor activity. CD73 expression on human and mouse PDAC tumor cells also protected against DNA damage induced by gemcitabine and irradiation. Accordingly, large-scale pharmacogenomic analyses of human PDAC cell lines revealed significant associations between CD73 expression and gemcitabine chemoresistance. Strikingly, increased DNA damage in CD73-deficient tumor cells associated with activation of the cGAS-STING pathway. Moreover, cGAS expression in mouse KPC tumor cells was required for antitumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression.
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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.