ArticleJournal of virology2012
The histone deacetylase inhibitor valproic acid lessens NK cell action against oncolytic virus-infected glioblastoma cells by inhibition of STAT5/T-BET signaling and generation of gamma interferon.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 91 citations in OpenAlex.
- Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing.PLoS pathogens · 2014Trial
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Oncolytic HSV and cancer drug interactions: Current clinical status and future directions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Targeting Latent HIV Reservoirs: Effectiveness of Combination Therapy with HDAC and PARP Inhibitors.Viruses · 2025Article
- Emerging Therapies for Glioblastoma.Cancers · 2024Review
- Quantitative and Qualitative Distinctions between HIV-1 and SIV Reservoirs: Implications for HIV-1 Cure-Related Studies.Viruses · 2024Review
- The emerging field of oncolytic virus-based cancer immunotherapy.Trends in cancer · 2023Review
- Article
- Histone deacetylase inhibitors enhance oncolytic herpes simplex virus therapy for malignant meningioma.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Natural killer cell homing and trafficking in tissues and tumors: from biology to application.Signal transduction and targeted therapy · 2022Review
- Histone modifiers at the crossroads of oncolytic and oncogenic viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Delivering Glioblastoma a Kick-DGKα Inhibition as a Promising Therapeutic Strategy for GBM.Cancers · 2022Review
- Tumor-Associated Macrophages/Microglia in Glioblastoma Oncolytic Virotherapy: A Double-Edged Sword.International journal of molecular sciences · 2022Review
- Review
- Review
- Review
- Natural Killer Cells and Anti-Cancer Therapies: Reciprocal Effects on Immune Function and Therapeutic Response.Cancers · 2021Review
- Parvovirus-Based Combinatorial Immunotherapy: A Reinforced Therapeutic Strategy against Poor-Prognosis Solid Cancers.Cancers · 2021Review
- T Helper Cell Lineage-Defining Transcription Factors: Potent Targets for Specific GVHD Therapy?Frontiers in immunology · 2021Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Tumor virotherapy has been and continues to be used in clinical trials. One barrier to effective viral oncolysis, consisting of the interferon (IFN) response induced by viral infection, is inhibited by valproic acid (VPA) and other histone deacetylase inhibitors (HDACi). Innate immune cell recruitment and activation have been shown to be deleterious to the efficacy of oncolytic herpes simplex virus (oHSV) infection, and in this report we demonstrate that VPA limits this deleterious response. VPA, administered prior to oHSV inoculation in an orthotopic glioblastoma mouse model, resulted in a decline in NK and macrophage recruitment into tumor-bearing brains at 6 and 24 h post-oHSV infection. Interestingly, there was a robust rebound of recruitment of these cells at 72 h post-oHSV infection. The observed initial decline in immune cell recruitment was accompanied by a reduction in their activation status. VPA was also found to have a profound immunosuppressive effect on human NK cells in vitro. NK cytotoxicity was abrogated following exposure to VPA, consistent with downmodulation of cytotoxic gene expression of granzyme B and perforin at the mRNA and protein levels. In addition, suppression of gamma IFN (IFN-γ) production by VPA was associated with decreased STAT5 phosphorylation and dampened T-BET expression. Despite VPA-mediated immune suppression, mice were not at significantly increased risk for HSV encephalitis. These findings indicate that one of the avenues by which VPA enhances oHSV efficacy is through initial suppression of immune cell recruitment and inhibition of inflammatory cell pathways within NK cells.
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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.