ArticleScientific reports2021
4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting SMYD2 improves immunotherapy response in experimental hepatocellular carcinoma.Molecular therapy. Oncology · 2026Article
- 4-Methylumbelliferone Modulates CAIX to Mitigate Hypoxia-Driven Dysregulation and Enhance PD-1 Immunotherapy in Lung Cancer.International journal of molecular sciences · 2025Article
- Hyaluronic Acid in Liver Fibrosis: Role in Inflammation, Tissue Remodeling, and Disease Progression.International journal of molecular sciences · 2025Review
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Macrophage polarization in hepatocellular carcinoma: a lncRNA-centric perspective on tumor progression and metastasis.Clinical and experimental medicine · 2025Review
- Extracellular matrix stiffness and tumor-associated macrophage polarization: new fields affecting immune exclusion.Cancer immunology, immunotherapy : CII · 2024Review
- Combined Effects of Anti-PD-L1 and Nanosonodynamic Therapy on HCC Immune Activation in Mice: An Investigation.International journal of nanomedicine · 2024Article
- Effects of Hyaluronan on Breast Cancer Aggressiveness.Cancers · 2023Review
- 4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.International journal of molecular sciences · 2023Article
- New hope for tumor immunotherapy: the macrophage-related "do not eat me" signaling pathway.Frontiers in pharmacology · 2023Review
- Potential of Compounds Originating from the Nature to Act in Hepatocellular Carcinoma Therapy by Targeting the Tumor Immunosuppressive Microenvironment: A Review.Molecules (Basel, Switzerland) · 2022Review
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma.Cell reports · 2022Article
- In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling.Cancers · 2021Review
- Macrophage Polarization and Its Role in Liver Disease.Frontiers in immunology · 2021Review
- Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) arises in the setting of advanced liver fibrosis, a dynamic and complex inflammatory disease. The tumor microenvironment (TME) is a mixture of cellular components including cancer cells, cancer stem cells (CSCs), tumor-associated macrophages (TAM), and dendritic cells (DCs), which might drive to tumor progression and resistance to therapies. In this work, we study the effects of 4-methylumbelliferone (4Mu) on TME and how this change could be exploited to promote a potent immune response against HCC. First, we observed that 4Mu therapy induced a switch of hepatic macrophages (Mϕ) towards an M1 type profile, and HCC cells (Hepa129 cells) exposed to conditioned medium (CM) derived from Mϕ treated with 4Mu showed reduced expression of several CSCs markers and aggressiveness. HCC cells incubated with CM derived from Mϕ treated with 4Mu grew in immunosuppressed mice while presented delayed tumor progression in immunocompetent mice. HCC cells treated with 4Mu were more susceptible to phagocytosis by DCs, and when DCs were pulsed with HCC cells previously treated with 4Mu displayed a potent antitumoral effect in therapeutic vaccination protocols. In conclusion, 4Mu has the ability to modulate TME into a less hostile milieu and to potentiate immunotherapeutic strategies against HCC.
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