ArticleHepatology international2014
Soluble FGL2, a novel effector molecule of activated hepatic stellate cells, regulates T-cell function in cirrhotic patients with hepatocellular carcinoma.
Article in Hepatology international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma.Cell communication and signaling : CCS · 2026Article
- Macrophage-derived Fgl2 dampens antitumor immunity through regulation of FcγRIIB+CD8+ T cells in melanoma.JCI insight · 2025Article
- CD8Nature communications · 2024Article
- FGL1 and FGL2: emerging regulators of liver health and disease.Biomarker research · 2024Review
- Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis.The Journal of clinical investigation · 2022Article
- Article
- Regulatory T cells induce polarization of pro-repair macrophages by secreting sFGL2 into the endometriotic milieu.Communications biology · 2021Article
- The Scavenger Function of Liver Sinusoidal Endothelial Cells in Health and Disease.Frontiers in physiology · 2021Review
- Fibrinogen-Like Protein 2 (FGL2) is a Novel Biomarker for Clinical Prediction of Human Breast Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- The Diverse Functions of the Ubiquitous Fcγ Receptors and Their Unique Constituent, FcRγ Subunit.Pathogens (Basel, Switzerland) · 2020Review
- Long Non-coding RNA FENDRR Acts as a miR-423-5p Sponge to Suppress the Treg-Mediated Immune Escape of Hepatocellular Carcinoma Cells.Molecular therapy. Nucleic acids · 2019Article
- Soluble fibrinogen-like protein 2 promotes the growth of hepatocellular carcinoma via attenuating dendritic cell-mediated cytotoxic T cell activity.Journal of experimental & clinical cancer research : CR · 2019Article
- Fc gamma RIIb expression levels in human liver sinusoidal endothelial cells during progression of non-alcoholic fatty liver disease.PloS one · 2019Article
- Soluble fibrinogen-like protein 2 levels in patients with hepatitis B virus-related liver diseases.BMC infectious diseases · 2018Article
- Activation of Hepatic Stellate Cells During Liver Carcinogenesis Requires Fibrinogen/Integrin αvβ5 in Zebrafish.Neoplasia (New York, N.Y.) · 2018Article
- Soluble fibrinogen like protein 2 (sFGL2), the novel effector molecule for immunoregulation.Oncotarget · 2017Review
- Stroma-derived Fibrinogen-like Protein 2 Activates Cancer-associated Fibroblasts to Promote Tumor Growth in Lung Cancer.International journal of biological sciences · 2017Article
- MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- A disparate subset of double-negative T cells contributes to the outcome of murine fulminant viral hepatitis via effector molecule fibrinogen-like protein 2.Immunologic research · 2016Article
- Activated hepatic stellate cells promote liver cancer by induction of myeloid-derived suppressor cells through cyclooxygenase-2.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC).
methodsSerum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry. T-cells purified from HCC patients using magnetic beads were cultured with LX2 cells at different ratios with anti-CD3-stimulating or FGL2-blocking antibodies. The proliferation index (PI) of CD8 + T cells was assessed by flow cytometry, and the secretion of IFN-γ was measured by ELISA.
resultssFGL2 levels are significantly higher in patients with HCC or LC compared with those with CHB (p = 0.0039/p = 0.0020). Among HCC patients, those with cirrhosis exhibited significantly higher levels of sFGL2 compared with non-cirrhotic individuals (p = 0.0108). The expressions of FGL2 and α-SMA overlapped in HSCs in liver specimens. FGL2 protein secreted by LX2 cells inhibited T-cell proliferation of HCC patients in a dose-dependent manner in vitro. The PI of CD8 + T cells was significantly enhanced following addition of FGL2 antibody to the culture system (LX2/T-cell ratio of 1:10, p = 0.002). The level of IFN-γ in mixed cultures was inversely correlated with the number of HSCs and was reversed by incubation with FGL2 blocking antibody.
conclusionsFGL2 protein is a novel effector molecule of activated HSCs, which suppresses CD8 + T cell proliferation and interferon-γ production, and it subsequently might contribute to immune suppression during fibrosis and tumorigenesis in the liver.
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