ArticleJournal of translational medicine2006
Up-regulation of HLA class-I antigen expression and antigen-specific CTL response in cervical cancer cells by the demethylating agent hydralazine and the histone deacetylase inhibitor valproic acid.
Article in Journal of translational medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.Medical oncology (Northwood, London, England) · 2011Trial
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- Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.Journal of experimental & clinical cancer research : CR · 2025Review
- Mechanistic insights into resistance mechanisms to T cell engagers.Frontiers in immunology · 2025Review
- Transcriptomic profiling of peripheral blood cells in HPV-associated carcinoma patients receiving combined valproic acid and avelumab.Molecular oncology · 2024Article
- Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures.Cell reports · 2024Article
- Challenges and solutions for therapeutic TCR-based agents.Immunological reviews · 2023Review
- Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods.Pharmaceutics · 2023Article
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- Azacitidine and lenalidomide combination: a novel relapse prophylaxis regimen after allogeneic hematopoietic stem-cell transplantation in patients with acute myeloid leukemia.Frontiers in immunology · 2023Article
- Derivation of functional trophoblast stem cells from primed human pluripotent stem cells.Stem cell reports · 2022Article
- HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation.Frontiers in immunology · 2022Review
- Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response.Frontiers in immunology · 2022Review
- Review
- Evidence of Antitumor and Antimetastatic Potential of Induced Pluripotent Stem Cell-Based Vaccines in Cancer Immunotherapy.Frontiers in medicine · 2021Article
- Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation.Frontiers in immunology · 2021Review
- Article
- MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy.Cancers · 2020Review
- Inhibition of Histone Deacetylase (HDAC) Enhances Checkpoint Blockade Efficacy by Rendering Bladder Cancer Cells Visible for T Cell-Mediated Destruction.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA hypermethylation and histone deacetylation are epigenetic events that contribute to the absence or downregulated expression of different components of the tumor recognition complex. These events affect the processing and presentation of antigenic peptides to CTLs by HLA class-I molecules. In this work evaluated the effect of the DNA hypomethylating agent hydralazine and the histone deacetylase inhibitor valproic acid, on the expression of HLA class-I molecules and on the antigen-specific immune recognition of cervical cancer cells.
methodsCell lines C33A (HPV-), CaSki (HPV-16+) and MS751 (HPV-18+) were treated with hydralazine and valproic acid to assess the expression of HLA class-I molecules by flow cytometry and RT-PCR. Promoter methylation of HLA class-I -A, -B and C, was also evaluated by Methylation-Specific PCR. Primary cervical tumors of four HLA-A*0201 allele patients were typed for HPV and their CTL's stimulated in vitro with the T2 cell line previously loaded with 50 microM of the HPV peptides. Cytotoxicity of stimulated CTL's was assayed against Caski and MS751 cells pre-treated with hydralazine and valproic acid.
resultsValproic acid and hydralazine/valproic acid up-regulated the constitutive HLA class-I expression as evaluated by flow cytometry and RT-PCR despite constitutive promoter demethylation at these loci. Hydralazine and valproic acid in combination but no IFN-gamma hyperacetylated histone H4 as evaluated by ChiP assay. The antigenic immune recognition of CaSki and MS751 cells by CTLs specific to HPV-16/18 E6 and E7-derived epitopes, was increased by VA and H/VA and the combination of H/VA/IFN-gamma.
conclusionThese results support the potential use of hydralazine and valproic acid as an adjuvant for immune intervention in cervical cancer patients whenever clinical protocols based on tumor antigen recognition is desirable, like in those cases where the application of E6 and E7 based therapeutic vaccines is used.
Identifiers
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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.