ArticleProceedings of the National Academy of Sciences of the United States of America2014
TGF-β-inducible microRNA-183 silences tumor-associated natural killer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 2 of them syntheses that pooled it.
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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
150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 211 citations in OpenAlex.
- Effects of air pollution on the development and progression of digestive diseases: an umbrella review of systematic reviews and meta-analyses.BMC public health · 2025Pooled it
- Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression.Frontiers in immunology · 2021Pooled it
- Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.Signal transduction and targeted therapy · 2024Trial
- Platelets as regulators of anti-tumor immunity: mechanisms and clinical implications.Cancer metastasis reviews · 2026Review
- ITPKB is a conserved regulator of natural killer cell desensitization/education that constrains antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Circumventing Ewing sarcoma tumor microenvironment resistance by IL1RAP CAR-modified TGFβ1-imprinted natural killer cells in combination with IL-15 agonist and anti-GD2 antibody.Journal for immunotherapy of cancer · 2026Article
- Osteopontin-driven TGF-β1 signaling via integrin αvβ3-NF-κB axis impairs NK cell function in head and neck squamous cell carcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Cancer-associated fibroblasts: enablers of tumor drug resistance.Journal of translational medicine · 2026Review
- Thrombocytosis in cancer patients: when more is not better-in fact, the opposite.Cancer metastasis reviews · 2026Review
- Targeting Oxidative and Nitrosative Stress: Mechanistic Insights and Therapeutic Strategies for Radiation-Induced Lung Injury.Journal of inflammation research · 2026Review
- iPSC-derived CAR-NK extracellular vesicles for non-small cell lung cancer: evidence, engineering, and translational barriers.Frontiers in immunology · 2026Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- MicroRNA-mediated regulation of natural killer cells development, effector functions, and antitumor responses.Cancer cell international · 2025Review
- Human miRNAs in Cancer: Statistical Trends and Cross Kingdom Approach.International journal of molecular sciences · 2025Article
- The Role of Reactive Oxygen Species in Lung Cancer Development: Nanomedicine as a Therapeutic Strategy.Biomolecules · 2025Review
- Review
- Role and Significance of MicroRNAs in the Relationship Between Obesity and Cancer.Balkan medical journal · 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
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Transforming growth factor β1 (TGF-β), enriched in the tumor microenvironment and broadly immunosuppressive, inhibits natural killer (NK) cell function by yet-unknown mechanisms. Here we show that TGF-β-treated human NK cells exhibit reduced tumor cytolysis and abrogated perforin polarization to the immune synapse. This result was accompanied by loss of surface expression of activating killer Ig-like receptor 2DS4 and NKp44, despite intact cytoplasmic stores of these receptors. Instead, TGF-β depleted DNAX activating protein 12 kDa (DAP12), which is critical for surface NK receptor stabilization and downstream signal transduction. Mechanistic analysis revealed that TGF-β induced microRNA (miR)-183 to repress DAP12 transcription/translation. This pathway was confirmed with luciferase reporter constructs bearing the DAP12 3' untranslated region as well as in human NK cells by use of sense and antisense miR-183. Moreover, we documented reduced DAP12 expression in tumor-associated NK cells in lung cancer patients, illustrating this pathway to be consistently perturbed in the human tumor microenvironment.
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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.