ArticlePharmaceutical research2015
The narrow-spectrum HDAC inhibitor entinostat enhances NKG2D expression without NK cell toxicity, leading to enhanced recognition of cancer cells.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 106 citations in OpenAlex.
- Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial.Nature communications · 2024Trial
- Review
- Targeting the MICA/B-NKG2D axis in cancer: from molecular structure to immunotherapeutic strategies-a narrative review.Translational cancer research · 2026Review
- Epigenetic remodeling in sarcoma promotes T-cell infiltration via modulation of the Hippo pathway.Journal for immunotherapy of cancer · 2026Article
- Epigenetic Alterations in Colitis-Associated Colorectal Cancer.Epigenomes · 2026Review
- Combinatorial therapy with resveratrol sensitizes glioblastoma to NKG2D CAR-T cells.Frontiers in immunology · 2026Article
- Development and evaluation of an inhalable nanoemulsion system for enhancing NK cell function against osteosarcoma pulmonary metastases.Frontiers in immunology · 2026Article
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- The Metabolic Regulation of the NKG2D-Positive NK and T Cells and Their Role in Disease Progression.Biomolecules · 2025Review
- Epigenetic modulation elicits an NK cell-mediated immune response in urothelial carcinoma.Molecular medicine (Cambridge, Mass.) · 2025Article
- Targeting the HLA-E-NKG2A axis in combination with MS-275 enhances NK cell-based immunotherapy against DMG.Journal of experimental & clinical cancer research : CR · 2025Article
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- Review
- Combining ERAP1 silencing and entinostat therapy to overcome resistance to cancer immunotherapy in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Reprogramming natural killer cells for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- It Takes Two to Tango: The Interplay between Prostate Cancer and Its Microenvironment from an Epigenetic Perspective.Cancers · 2024Review
- Inhibition of histone deacetylase promotes a neuroprotective mechanism in an experimental model of Parkinson's disease.Archives of medical science : AMS · 2024Article
- Synergistic integration of histone deacetylase inhibitors apparently enhances the cytokine-induced killer cell efficiency in multiple myeloma via the NKG2D pathway.Clinical & translational immunology · 2024Article
- Epigenetic regulation of NKG2D ligand and the rise of NK cell-based immunotherapy for cancer treatment.Frontiers in oncology · 2024Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeNatural killer (NK) cell cytotoxicity correlates with the ligation of activating receptors (e.g., NKG2D) by their ligands (e.g., MHC class I-related chains [MIC] A and B) on target cells. Histone deacetylase inhibitors (HDACi) at high concentrations inhibit tumor growth and can increase NKG2D ligand expression on tumor targets, but are widely regarded as toxic to NK cells.
methodsWe investigated the mechanism of entinostat, a benzamide-derivative narrow-spectrum HDACi, in augmenting the cytotoxicity of NK cells against human colon carcinoma and sarcoma by assessing gene and protein expression, histone acetylation, and cytotoxicity in in vitro and murine models.
resultsWe observed that entinostat dose- and time-dependent increase in MIC expression in tumor targets and NKG2D in primary human NK cells, both correlating with increased acetylated histone 3 (AcH3) binding to associated promoters. Entinostat pretreatment of colon carcinoma and sarcoma cells, NK cells, or both led to enhanced overall cytotoxicity in vitro, which was reversed by NKG2D blockade, and inhibited growth of tumor xenografts. Lastly, we showed decreased expression of MICA and ULBP2 transcription in primary human osteosarcoma.
conclusionsEntinostat enhances NK cell killing of cancer cells through upregulation of both NKG2D and its ligands, suggesting an attractive approach for augmenting NK cell immunotherapy of solid tumors such as colon carcinoma and sarcomas.
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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.