ArticleJCI insight2024
Hepatocyte-derived FGL1 accelerates liver metastasis and tumor growth by inhibiting CD8+ T and NK cells.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Hepatokine FGL1 drives endothelial injury and atherogenesisActa pharmaceutica Sinica. B · 2026Article
- FGL-1 plasma levels correlate with markers of inflammation and severe disease during SARS-CoV-2 infection.Communications medicine · 2026Article
- Review
- The unseen architects of metastasis: coagulation factors in pre-metastatic niche development.Cell communication and signaling : CCS · 2026Review
- Optimizing anti-PI3Kδ and anti-LAG-3 immunotherapy dosing regimens in a mouse model of triple-negative breast cancer improves outcome by removing treatment-related adverse events.Journal for immunotherapy of cancer · 2026Article
- The FGL1-LAG-3 axis attenuates melanoma-induced cachexia in mice.Cancer & metabolism · 2026Article
- Lymphocyte activation gene 3 in autoimmune disease: from molecular mechanisms to clinical applications.Frontiers in immunology · 2026Review
- PTM-Related Signatures Predict Lymph Node Metastasis and Shape Microenvironment in Hepatocellular Carcinoma: A Single-Cell and Bulk Integrated Analysis.Journal of hepatocellular carcinoma · 2026Article
- Unraveling fibrinogen-like protein 1's role in immune regulation.Frontiers in immunology · 2026Review
- Navigating the Tumor Microenvironment in Colorectal Liver Metastasis: Barriers to Therapy and Emerging Opportunities.Oncology research · 2026Review
- Exploring new frontiers in LAG-3 biology and therapeutics.Trends in pharmacological sciences · 2025Review
- Review
- Identification of CENPM as a key gene driving adrenocortical carcinoma metastasis via physical interaction with immune checkpoint ligand FGL1.Clinical and translational medicine · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrinogen-like protein 1 (FGL1) contributes to the proliferation and metabolism of hepatocytes; however, as a major ligand of the immune checkpoint, its role in the liver regional immune microenvironment is poorly understood. Hepatocytes specifically and highly expressed FGL1 under normal physiological conditions. Increases in hepatic CD8+ T and NK cell numbers and functions were found in Fgl1-deficient (Fgl1-/-) mice, but not in the spleen or lymph node, similar to findings in anti-FGL1 mAb-treated wild-type mice. Furthermore, Fgl1 deficiency or anti-FGL1 mAb blockade restrained liver metastasis and slowed the growth of orthotopic tumors, with significantly prolonged survival of tumor-bearing mice. Tumor-infiltrating hepatic CD8+ T and NK cells upregulated the expression of lymphocyte activation gene-3 (LAG-3) and exhibited stronger antitumor activities after anti-FGL1 treatment. The antitumor efficacy of FGL1 blockade depended on cytotoxic T lymphocytes and NK cells, demonstrated by using a cell-deficient mouse model and cell transfer in vivo. In vitro, FGL1 directly inhibited hepatic T and NK cells related to the receptor LAG-3. In conclusion, hepatocyte-derived FGL1 played critical immunoregulatory roles in the liver and contributed to liver metastasis and tumor growth by inhibiting CD8+ T and NK cell functions via the receptor LAG-3, providing a new strategy for liver cancer immunotherapy.
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