ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Tumor Microenvironment Remodeling by 4-Methylumbelliferone Boosts the Antitumor Effect of Combined Immunotherapy in Murine Colorectal Carcinoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Label-Free Direct Detection of 4MU by Plasmon Enhanced Fluorescence Sensing Based on Ag@SiOJournal of fluorescence · 2025Article
- 4-Methylumbelliferone Modulates CAIX to Mitigate Hypoxia-Driven Dysregulation and Enhance PD-1 Immunotherapy in Lung Cancer.International journal of molecular sciences · 2025Article
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
- Coumarins in the tumor-immune application: from molecular mechanisms to therapeutic innovations.Frontiers in immunology · 2025Review
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- Deciphering Drug Resistance: Investigating the Emerging Role of Hyaluronan Metabolism and Signaling and Tumor Extracellular Matrix in Cancer Chemotherapy.International journal of molecular sciences · 2024Review
- Small molecule inhibitors of mammalian glycosylation.Matrix biology plus · 2022Article
- Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer.Nature communications · 2022Article
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy.Frontiers in oncology · 2021Review
- Hyaluronic Acid Binding to TLR4 Promotes Proliferation and Blocks Apoptosis in Colon Cancer.Molecular cancer therapeutics · 2019Article
- Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy.Frontiers in molecular biosciences · 2019Review
- 4Mu Decreases CD47 Expression on Hepatic Cancer Stem Cells and Primes a Potent Antitumor T Cell Response Induced by Interleukin-12.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Glycogen debranching enzyme (AGL) is a novel regulator of non-small cell lung cancer growth.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously demonstrated that a low dose of cyclophosphamide (Cy) combined with gene therapy of interleukin-12 (AdIL-12) has a synergistic, although limited, antitumoral effect in mice with colorectal carcinoma. The main mechanism involved in the efficacy of Cy+AdIL-12 was the induction of a specific immune response mediated by cytotoxic T lymphocytes. Our current aims were to evaluate the effects of 4-methylumbelliferone (4Mu), a selective inhibitor of hyaluronan (HA) synthesis, on tumor microenvironment (TME) and to investigate how 4Mu affects the therapeutic efficacy of Cy+AdIL-12. The results showed that 4Mu significantly reduced the amount of tumoral HA leading to a significant decrease in tumor interstitial pressure (TIP). As a consequence, tumor perfusion was improved allowing an increased adenoviral transgene expression. In addition, treatment with 4Mu boosted the number of cytotoxic T lymphocytes that reach the tumor after adoptive transfer resulting in a potent inhibition of tumor growth. Importantly, we observed complete tumor regression in 75% of mice when 4Mu was administrated in combination with Cy+AdIL-12. The triple combination 4Mu+Cy+AdIL-12 also induced a shift toward antiangiogenic factors production in tumor milieu. Our results showed that TME remodeling is an interesting strategy to increase the efficacy of anticancer immunotherapies based on gene and/or cell therapy.
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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.