ArticleMolecular cancer2024
Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Combination of exosome vaccines, lenvatinib, and anti-PD-1 eradicates tumor in autochthonous hepatocellular carcinoma mice.Cell reports. Medicine · 2026Article
- When the Liver Flares: Inflammatory and Immunometabolic Mechanisms Driving the Transition from MASLD to MASH.Inflammation · 2026Review
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- HIF-2α induction in de novo lipogenesis in metabolic dysfunction-associated steatohepatitis is dependent on IL-21 signaling.The Journal of biological chemistry · 2026Article
- Integrated Bioinformatics Analysis Revealing that the NSDHL Gene Might Be Associated with the Progression of Western HFD/SW-Induced Hepatocellular CarcinomaEndocrine, metabolic & immune disorders drug targets · 2026Article
- Development and Assessment of a Novel Palmitoylation-Related lncRNA Signature for Prognosis and Immune Landscape in Hepatocellular Carcinoma.Oncology research · 2026Article
- Immunopathogenic mechanisms and immunoregulatory therapies in MASLD.Cellular & molecular immunology · 2025Review
- Single-cell transcriptome reveals the reprogramming of immune microenvironment during the transition from MASH to HCC.Molecular cancer · 2025Article
- Acetyl-CoA synthetase 2 alleviates brain injury following cardiac arrest by promoting autophagy in brain microvascular endothelial cells.Cellular and molecular life sciences : CMLS · 2025Article
- B cells and tertiary lymphoid structures in tumors: immunity cycle, clinical impact, and therapeutic applications.Theranostics · 2025Review
- Dynamic crosstalk between HSCs and liver microenvironment: multicellular interactions in the regulation of liver fibrosis.Frontiers in cell and developmental biology · 2025Review
- Immunotherapy resistance in MASLD-related hepatocellular carcinoma: special immune microenvironment and gut microbiota.International journal of biological sciences · 2025Review
- The dual immunomodulatory role of B cells in tumorigenesis: mechanisms, microenvironment crosstalk, and therapeutic implications.Frontiers in immunology · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundDysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC.
methodsThe clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA
resultsHCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8
conclusionsIL-21R plays a cancer-promoting role by inducing IgA
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