ArticleCancer immunology, immunotherapy : CII2018
The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Major histocompatibility complex II serves as a prognostic biomarker in resectable pulmonary sarcomatoid carcinoma: development of a prediction model.Translational lung cancer research · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.Cancer innovation · 2025Review
- A propidium iodide-basedAntimicrobial agents and chemotherapy · 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
- Comprehensive Investigation of a Tyrosine Kinase Inhibitor-Resistant GeneWorld journal of oncology · 2025Article
- Targeted intervention of tumor microenvironment with HDAC inhibitors and their combination therapy strategies.European journal of medical research · 2025Review
- Expanding the immunotherapy universe in extensive-stage small cell lung cancer: from chemoimmunotherapy backbone to next-wave combinations.Frontiers in immunology · 2025Review
- Article
- A Novel Liver Cancer-Selective Histone Deacetylase Inhibitor Is Effective against Hepatocellular Carcinoma and Induces Durable Responses with Immunotherapy.ACS pharmacology & translational science · 2024Article
- HDAC inhibitor SAHA enhances antitumor immunity via the HDAC1/JAK1/FGL1 axis in lung adenocarcinoma.Journal for immunotherapy of cancer · 2024Article
- Targeting histone modifiers in bladder cancer therapy - preclinical and clinical evidence.Nature reviews. Urology · 2024Review
- Article
- Transcriptome profiling and characterization of peritoneal metastasis ovarian cancer xenografts in humanized mice.Scientific reports · 2024Article
- PD-L1 Expression in Neoplastic and Immune Cells of Thymic Epithelial Tumors: Correlations with Disease Characteristics and HDAC Expression.Biomedicines · 2024Article
- Emerging therapeutic strategies in cancer therapy by HDAC inhibition as the chemotherapeutic potent and epigenetic regulator.Medical oncology (Northwood, London, England) · 2024Review
- Combination Therapy with Immune Checkpoint Inhibitors and Histone Deacetylase Inhibitors or Alkylating Agents.Cancer management and research · 2024Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells. Mocetinostat upregulated PD-L1 and antigen presentation genes including class I and II human leukocyte antigen (HLA) family members in a panel of NSCLC cell lines in vitro. Mocetinostat target gene promoters were occupied by a class I HDAC and exhibited increased active histone marks after mocetinostat treatment. Mocetinostat synergized with interferon γ (IFN-γ) in regulating class II transactivator (CIITA), a master regulator of class II HLA gene expression. In a syngeneic tumor model, mocetinostat decreased intratumoral T-regulatory cells (Tregs) and potentially myeloid-derived suppressor cell (MDSC) populations and increased intratumoral CD8+ populations. In ex vivo assays, patient-derived, mocetinostat-treated Tregs also showed significant down regulation of FOXP3 and HELIOS. The combination of mocetinostat and a murine PD-L1 antibody antagonist demonstrated increased anti-tumor activity compared to either therapy alone in two syngeneic tumor models. Together, these data provide evidence that mocetinostat modulates immune-related genes in tumor cells as well as immune cell types in the tumor microenvironment and enhances checkpoint inhibitor therapy.
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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.