ArticleCellular and molecular life sciences : CMLS2024
Disrupting Smad3 potentiates immunostimulatory function of NK cells against lung carcinoma by promoting GM-CSF production.
Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed.
- Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial.Nature communications · 2024Trial
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- Epitranscriptomic silencing of the ZC3H13/mJournal of experimental & clinical cancer research : CR · 2026Article
- Understanding the dual role of granulocyte-macrophage colony-stimulating factor in the lung cancer tumor microenvironment and its therapeutic implications.Translational lung cancer research · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application.Journal of inflammation research · 2025Review
- circWWC3 enhances the progression of triple-negative breast cancer by interacting with vimentin to regulate the secretion of CSF2.Frontiers in immunology · 2025Article
- NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025Review
- Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Through Smad3-dependent signalings, transforming growth factor-β (TGF-β) suppresses the development, maturation, cytokine productions and cytolytic functions of NK cells in cancer. Silencing Smad3 remarkably restores the cytotoxicity of NK-92 against cancer in TGF-β-rich microenvironment, but its effects on the immunoregulatory functions of NK cells remain obscure. In this study, we identified Smad3 functioned as a transcriptional repressor for CSF2 (GM-CSF) in NK cells. Therefore, disrupting Smad3 largely mitigated TGF-β-mediated suppression on GM-CSF production by NK cells. Furthermore, silencing GM-CSF in Smad3 knockout NK cells substantially impaired their anti-lung carcinoma effects. In-depth study demonstrated that NK-derived GM-CSF strengthened T cell immune responses by stimulating dendritic cell differentiation and M1 macrophage polarization. Meanwhile, NK-derived GM-CSF promoted the survival of neutrophils, which in turn facilitated the terminal maturation of NK cells, and subsequently boosted NK-cell mediated cytotoxicity against lung carcinoma. Thus, Smad3-silenced NK-92 (NK-92-S3KD) may serve as a promising immunoadjuvant therapy with clinical translational value given its robust cytotoxicity against malignant cells and immunostimulatory functions to reinforce the therapeutic effects of other immunotherapies.
Indexed as
Identifiers
What OpenQuestion holds
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.