ArticleJournal for immunotherapy of cancer2020
Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody-dependent cell-mediated phagocytosis.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- A systematic review of progress toward unlocking the power of epigenetics in breast cancer: latest updates and perspectives.Frontiers in pharmacology · 2025Pooled it
- Navigating the complexities of epigenetic dysregulation in breast cancer and its implication in therapeutic interventions: a comprehensive overview.Molecular and cellular biochemistry · 2026Review
- Repeated Valproic Acid Administration Fundamentally Ameliorated Cisplatin-Induced Mechanical Allodynia in Rats.International journal of molecular sciences · 2025Article
- Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Minireview on Nanosized Hypericin-Based Inducer of Immune Cell Death Under ROS-Based Therapies.International journal of nanomedicine · 2025Review
- The advances in targeting CD47/SIRPα "do not eat me" axis and their ongoing challenges as an anticancer therapy.Oncotarget · 2024Article
- Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.Heliyon · 2024Review
- Review
- Targeting HDAC6 improves anti-CD47 immunotherapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy.Cell death discovery · 2023Review
- Epigenetic Regulation in Breast Cancer: Insights on Epidrugs.Epigenomes · 2023Review
- Targeted inhibition of STAT3 induces immunogenic cell death of hepatocellular carcinoma cells via glycolysis.Molecular oncology · 2022Article
- Detailed Molecular Mechanisms Involved in Drug-Induced Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: An Update.Biomedicines · 2022Review
- Role of Fcγ receptors in HER2-targeted breast cancer therapy.Journal for immunotherapy of cancer · 2022Review
- Epigenetic modulation of antitumor immunity for improved cancer immunotherapy.Molecular cancer · 2021Review
- Review
- Systematic review of the immunological landscape of Wilms tumors.Molecular therapy oncolytics · 2021Review
- Vorinostat (SAHA) and Breast Cancer: An Overview.Cancers · 2021Review
- HDAC inhibition potentiates anti-tumor activity of macrophages and enhances anti-PD-L1-mediated tumor suppression.Oncogene · 2021Article
- Identification of Hypoxia-Immune-Related Gene Signatures and Construction of a Prognostic Model in Kidney Renal Clear Cell Carcinoma.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe monoclonal antibody (mAb) trastuzumab is part of the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. Antibody-dependent cell-mediated phagocytosis (ADCP) and cytotoxicity (ADCC) are major mechanisms of action of the mAb trastuzumab. Histone deacetylase inhibitors (HDACi), such as valproic acid (VPA) or vorinostat (SAHA), exert several immunostimulatory properties, which contribute at least in part to their anticancer effect. However, the impact of HDACi-induced immunostimulatory effects on trastuzumab-mediated anti-tumor immune response is not well characterized.
methodsWe analyzed the ADCP and ADCC activity of peripheral blood mononuclear cells (PBMCs) from age and gender-matched healthy volunteers (n=5) against HDACi-treated HER2-overexpressing breast cancer cells (SKBR3), using a well-established in vitro three-color imaging flow cytometry and flow cytometry approach.
resultsVPA and SAHA enhanced trastuzumab-mediated ADCP and trastuzumab-independent cytotoxicity. Mechanistically, VPA upregulated the activating antibody-binding receptor Fc-gamma receptor (FcγR) IIA (CD32A) on monocytes (CD14+). Moreover, VPA and SAHA downregulated the anti-apoptotic protein myeloid leukemia cell differentiation 1 (MCL1) in breast cancer cells. Additionally, VPA and SAHA induced an immunogenic cell death, characterized by the exposure of calreticulin (CALR), as well as decreased the "do not eat me" signal CD47 on tumor cells.
conclusionsHDACi VPA and SAHA increase trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity. The immunomodulatory activities of those HDACi support a rationale combined treatment approach with mAb for cancer treatment.
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