ArticleCancer immunology research2015
HDAC Inhibition Upregulates PD-1 Ligands in Melanoma and Augments Immunotherapy with PD-1 Blockade.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers, 1 of them a synthesis that pooled it.
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Who cites it
291 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Harnessing the immune system in the treatment of cutaneous T cell lymphomas.Frontiers in oncology · 2022Pooled it
- Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial.Nature cancer · 2025Trial
- The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma.Nature communications · 2021Trial
- CREBBP loss drives immune evasion by epigenetically silencing STING and MHC-I in small cell lung cancer.Science advances · 2026Article
- ClonalLife science alliance · 2026Article
- Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Single-Dose TACE-Like Injection of Sustained-Release Panobinostat/IL-12 Polymeric Microparticles is Effective in Preclinical Liver Cancer Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of chromatin remodeling and immunopharmacology in cancer therapy.Molecular medicine (Cambridge, Mass.) · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Vorinostat Potentiates Chemoimmunotherapy in Immune-Enriched Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SAHA Alters Macrophages in the Tumor-Immune Landscape in Preclinical Models of Triple-Negative Breast Cancer.Pharmaceutics · 2026Article
- A conceptual blueprint for "turning cold to hot" in Osteosarcoma: from TME stratification hypotheses to adaptive therapeutic prospects.Cell communication and signaling : CCS · 2026Review
- A Study on the Association Between Treatment Response to Atezolizumab Plus Bevacizumab Combination Therapy for Advanced Hepatocellular Carcinoma and Gut Microbiota.Microorganisms · 2026Article
- Gut Microbiota Biomarkers in Patients with Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors.Life (Basel, Switzerland) · 2026Review
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- TGF-β mediates epigenetic control of innate antiviral responses and SIV reservoir size.Nature immunology · 2026Article
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- The lactylation-immunosuppression network in cancer: driving a metabolic-epigenetic axis.Frontiers in immunology · 2026Review
231 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Expression of PD-1 ligands by tumors and interaction with PD-1-expressing T cells in the tumor microenvironment can result in tolerance. Therapies targeting this coinhibitory axis have proven clinically successful in the treatment of metastatic melanoma, non-small cell lung cancer, and other malignancies. Therapeutic agents targeting the epigenetic regulatory family of histone deacetylases (HDAC) have shown clinical success in the treatment of some hematologic malignancies. Beyond direct tumor cell cytotoxicity, HDAC inhibitors have also been shown to alter the immunogenicity and enhance antitumor immune responses. Here, we show that class I HDAC inhibitors upregulated the expression of PD-L1 and, to a lesser degree, PD-L2 in melanomas. Evaluation of human and murine cell lines and patient tumors treated with a variety of HDAC inhibitors in vitro displayed upregulation of these ligands. This upregulation was robust and durable, with enhanced expression lasting past 96 hours. These results were validated in vivo in a B16F10 syngeneic murine model. Mechanistically, HDAC inhibitor treatment resulted in rapid upregulation of histone acetylation of the PD-L1 gene leading to enhanced and durable gene expression. The efficacy of combining HDAC inhibition with PD-1 blockade for treatment of melanoma was also explored in a murine B16F10 model. Mice receiving combination therapy had a slower tumor progression and increased survival compared with control and single-agent treatments. These results highlight the ability of epigenetic modifiers to augment immunotherapies, providing a rationale for combining HDAC inhibitors with PD-1 blockade.
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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.