ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Targeting inflammatory macrophages rebuilds therapeutic efficacy of DOT1L inhibition in hepatocellular carcinoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Chromatin chronicles: Unlocking the therapeutic potential of histone modifiers in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.Translational oncology · 2026Review
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- Berberine Hydrochloride Inhibits the Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells by Regulating Amino Acid Metabolism.Anti-cancer agents in medicinal chemistry · 2026Article
- Epigenetic Regulation of Immune Responses in Endocrine-Related Cancers and Its Role in Immunotherapy.Cancers · 2025Review
- The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.British journal of cancer · 2025Review
- Tribbles Pseudokinase 3 Converts Sorafenib Therapy to Neutrophil-Mediated Lung Metastasis in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Histone modifications and metabolic reprogramming in tumor-associated macrophages: a potential target of tumor immunotherapy.Frontiers in immunology · 2025Review
- Lysine methylation modifications in tumor immunomodulation and immunotherapy: regulatory mechanisms and perspectives.Biomarker research · 2024Review
- Pan-Cancer Single-Cell and Spatial-Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- miRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
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Abstract
Epigenetic reprogramming is a promising therapeutic strategy for aggressive cancers, but its limitations in vivo remain unclear. Here, we showed, in detailed studies of data regarding 410 patients with human hepatocellular carcinoma (HCC), that increased histone methyltransferase DOT1L triggered epithelial-mesenchymal transition-mediated metastasis and served as a therapeutic target for human HCC. Unexpectedly, although targeting DOT1L in vitro abrogated the invasive potential of hepatoma cells, abrogation of DOT1L signals hardly affected the metastasis of hepatoma in vivo. Macrophages, which constitute the major cellular component of the stroma, abrogated the anti-metastatic effect of DOT1L targeting. Mechanistically, NF-κB signal elicited by macrophage inflammatory response operated via a non-epigenetic machinery to eliminate the therapeutic efficacy of DOT1L targeting. Importantly, therapeutic strategy combining DOT1L-targeted therapy with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited cancer regression. Moreover, we found that the densities of macrophages in HCC determined malignant cell DOT1L-associated clinical outcome of the patients. Our results provide insight into the crosstalk between epigenetic reprogramming and cancer microenvironments and suggest that strategies to influence the functional activities of inflammatory cells may benefit epigenetic reprogramming therapy.
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