ArticleThe Journal of clinical investigation2020
CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 202 citations in OpenAlex.
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- The tumor microenvironment in triple negative breast cancer and a strategy to improve responses to immunotherapy using cryoablation and immunostimulants.Cancer biology & therapy · 2026Review
- Ineffectiveness of immune checkpoint inhibitors in prostate cancer: is it just a question of '-mabs'?The Journal of pathology · 2026Review
- Review
- Enhanced CD33 CAR-NK cells secreting anti-CD73scFv overcome adenosine-mediated immunosuppression and improve anti-AML efficacy.Journal for immunotherapy of cancer · 2026Article
- Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Downregulation of B7-H4 contributes to the synergistic effect of USP2a-targeted/anti-PD-1 combination therapy in EGFR mutant lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Transcriptional networks weaving natural killer anti-tumor immune response.Molecular cancer · 2026Review
- Integration of tumor microenvironment and metabolic signatures reveals TMPI-defined prognostic and immunotherapy-relevant phenotypes in breast cancer.Frontiers in pharmacology · 2026Article
- 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
- Constructing a Pan-Cancer Prognostic Model via Machine Learning Based on Immunogenic Cell Death Genes and Identifying NT5E as a Biomarker in Head and Neck Cancer.Current issues in molecular biology · 2025Article
- Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.Journal of experimental & clinical cancer research : CR · 2025Review
- IPSC‑derived NK cells for immunotherapy and therapeutic perspective (Review).Molecular medicine reports · 2025Review
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
- Natural Killer Cell Activation Signature Identifies Cyclin B1/CDK1 as a Druggable Target to Overcome Natural Killer Cell Dysfunction and Tumor Invasiveness in Melanoma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- MGAT1-Guided complex N-Glycans on CD73 regulate immune evasion in triple-negative breast cancer.Nature communications · 2025Article
- CD103+CD56+ ILCs Are Associated with an Altered CD8+ T-cell Profile within the Tumor Microenvironment.Cancer immunology research · 2025Article
- Novel anti-CD73-IL-2v bispecific fusion protein augments antitumor immunity by alleviating immunosuppressive adenosine pathways in CD8Journal for immunotherapy of cancer · 2025Article
- Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer.Nature reviews. Drug discovery · 2025Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment.
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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.