ArticleInternational journal of molecular sciences2019
Hepatic Stellate Cells Enhance Liver Cancer Progression by Inducing Myeloid-Derived Suppressor Cells through Interleukin-6 Signaling.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Systemic Therapy for Advanced Hepatocellular Carcinoma in 2026: Current Standard-of-Care and Emerging Therapeutic Strategies.Journal of gastroenterology and hepatology · 2026Review
- Hepatitis C virus core protein-induced myeloid-derived suppressor cells promote hepatic fibrosis by regulating hepatic stellate cell function via TGF-β.Frontiers in immunology · 2026Article
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- Neutrophil Dynamics in Response to Cancer Therapies.Cancers · 2025Review
- Pathogenetic development, diagnosis and clinical therapeutic approaches for liver metastasis from colorectal cancer (Review).International journal of oncology · 2025Review
- Inflammation and Immunity in Liver Neoplasms: Implications for Future Therapeutic Strategies.Molecular cancer therapeutics · 2025Review
- Decoding the microbial-local immune dialogue in liver cancer: from ecological drivers to precision therapeutics.Frontiers in oncology · 2025Review
- Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4.Genes & diseases · 2024Article
- Neutrophils in Cancer immunotherapy: friends or foes?Molecular cancer · 2024Review
- The Roles of Myeloid-Derived Suppressor Cells in Liver Disease.Biomedicines · 2024Review
- Effects of Exercise-Induced Changes in Myokine Expression on the Tumor Microenvironment.Sports medicine international open · 2024Review
- Τ cell-mediated adaptive immunity in the transition from metabolic dysfunction-associated steatohepatitis to hepatocellular carcinoma.Frontiers in cell and developmental biology · 2024Review
- IL-6 Released from Hepatic Stellate Cells Promotes Glycolysis and Migration of HCC Through the JAK1/vWF/TGFB1 Axis.Journal of hepatocellular carcinoma · 2024Article
- Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment.Exploration of targeted anti-tumor therapy · 2024Review
- Immune landscape and immunotherapy of hepatocellular carcinoma: focus on innate and adaptive immune cells.Clinical and experimental medicine · 2023Review
- Friend or foe? The elusive role of hepatic stellate cells in liver cancer.Nature reviews. Gastroenterology & hepatology · 2023Review
- Expression of Cyclin E1 in hepatic stellate cells is critical for the induction and progression of liver fibrosis and hepatocellular carcinoma in mice.Cell death & disease · 2023Article
- Article
- Mechanism of exosomes in the tumor microenvironment in the abscopal effect (Review).International journal of oncology · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor microenvironment, which consists of fibroblasts, smooth muscle cells, endothelial cells, immune cells, epithelial cells, and extracellular matrices, plays a crucial role in tumor progression. Hepatic stellate cells (HSCs), a class of unique liver stromal cells, participate in immunomodulatory activities by inducing the apoptosis of effector T-cells, generation of regulatory T-cells, and development of myeloid-derived suppressor cells (MDSCs) to achieve long-term survival of islet allografts. This study provides in vitro and in vivo evidences that HSCs induce the generation of MDSCs to promote hepatocellular carcinoma (HCC) progression through interleukin (IL)-6 secretion. HSC-induced MDSCs highly expressed inducible nitric oxide synthase (iNOS) and arginase 1 mRNA and presented potent inhibitory T-cell immune responses in the tumor environment. Wild-type HSC-induced MDSCs expressed lower levels of CD40, CD86, and MHC II, and a higher level of B7-H1 surface molecules, as well as increased the production of iNOS and arginase I compared with MDSCs induced by IL-6-deficient HSCs in vitro. A murine-transplanted model of the liver tumor showed that HCCs cotransplanted with HSCs could significantly enhance the tumor area and detect more MDSCs compared with HCCs alone or HCCs cotransplanted with HSCs lacking IL-6. In conclusion, the results indicated that MDSCs are induced mainly by HSCs through IL-6 signaling and produce inhibitory enzymes to reduce T-cell immunity and then promote HCC progression within the tumor microenvironment. Therapies targeting the pathway involved in MDSC production or its immune-modulating pathways can serve as an alternative immunotherapy for HCC.
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