ArticleAmerican journal of cancer research2016
Epigenetic suppression of the antitumor cytotoxicity of NK cells by histone deacetylase inhibitor valproic acid.
Article in American journal of cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Review
- DNMT1 silencing induces KIR2DL1/2/3 expression via methylation to alleviate graft-Histology and histopathology · 2025Article
- Molecular Mediators of Neutrophil Primary Granule Release Following Acute Ischemic Stroke and their Associated Epigenetic Modulation by HDAC2.Molecular neurobiology · 2025Article
- Review
- CAR-NK cells: harnessing the power of natural killers for advanced cancer therapy.Frontiers in immunology · 2025Review
- Epigenetic remodeling of the immune landscape in cancer: therapeutic hurdles and opportunities.Journal of biomedical science · 2023Review
- Epigenetic modulations of immune cells: from normal development to tumor progression.International journal of biological sciences · 2023Review
- Epigenetic modulation and prostate cancer: Paving the way for NK cell anti-tumor immunity.Frontiers in immunology · 2023Review
- Valproic acid restricts mast cell activation by Listeria monocytogenes.Scientific reports · 2022Article
- LncRNA NCAL1 potentiates natural killer cell cytotoxicity through the Gab2-PI3K-AKT pathway.Frontiers in immunology · 2022Article
- Histone deacetylase inhibitors regulate vitamin C transporter functional expression in intestinal epithelial cells.The Journal of nutritional biochemistry · 2021Article
- Leveraging NKG2D Ligands in Immuno-Oncology.Frontiers in immunology · 2021Review
- Epigenetic Regulation of NK Cell-Mediated Antitumor Immunity.Frontiers in immunology · 2021Review
- Enhanced activation of human NK cells by drug-exposed hepatocytes.Archives of toxicology · 2020Article
- Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy.International journal of molecular sciences · 2019Review
- Exploring the Drug Repurposing Versatility of Valproic Acid as a Multifunctional Regulator of Innate and Adaptive Immune Cells.Journal of immunology research · 2019Review
- A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1.Genome biology · 2018Article
- Epigenetic mechanisms of tumor resistance to immunotherapy.Cellular and molecular life sciences : CMLS · 2018Review
- NKG2D Ligands-Critical Targets for Cancer Immune Escape and Therapy.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells play an essential role in the fight against tumor development. The therapeutic use of autologous NK cells has been exploited to treat human malignancies, yet only limited antitumor activity is observed in cancer patients. In this study, we sought to augment the antitumor activity of NK cells using epigenetic approaches. Four small molecules that have been known to promote epigenetic reprogramming were tested for their ability to enhance the activity of NK cells. Using a tumor cell lysis assay, we found that the DNA demethylating agent 5-azacytidine and vitamin C did not significantly affect the tumor killing ability of NK cells. The thyroid hormone triiodothyronine (T3) slightly increased the activity of NK cells. The histone deacetylase inhibitor valproic acid (VPA), however, inhibited NK cell lytic activity against leukemic cells in a dose-dependent manner. Pretreatment using VPA reduced IFNγ secretion, impaired CD107a degranulation, and induced apoptosis by activating the PD-1/PD-L1 pathway. VPA downregulated the expression of the activating receptor NKG2D (natural-killer group 2, member D) by inducing histone K9 hypermethylation and DNA methylation in the gene promoter. Histone deacetylase inhibitors have been developed as anticancer agents for use as monotherapies or in combination with other anticancer therapies. Our data suggest that the activity of histone deacetylase inhibitors on NK cell activity should be considered in drug development.
Indexed as
Identifiers
27152238PMC4851840W2346386619What 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.