ArticleImmunology and cell biology2016
Hepatoma cell-derived leptin downregulates the immunosuppressive function of regulatory T-cells to enhance the anti-tumor activity of CD8+ T-cells.
Article in Immunology and cell biology, 2016. 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, 23 citations in OpenAlex.
- Exploring the Role of GITR/GITRL Signaling: From Liver Disease to Hepatocellular Carcinoma.Cancers · 2024Review
- The regulation of hypoxia-related lncRNAs in hepatocellular carcinoma.Discover oncology · 2024Review
- Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma.Frontiers in immunology · 2023Review
- Perindopril sensitizes hepatocellular carcinoma to chemotherapy: A possible role of leptin / Wnt/ β-catenin axis with subsequent inhibition of liver cancer stem cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Understanding the Role of Metabolic Syndrome as a Risk Factor for Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2022Review
- Leptin Deficiency May Influence the Divergence of Cell-Mediated Immunity Between Lepromatous and Tuberculoid Leprosy Patients.Journal of inflammation research · 2022Review
- Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC.International journal of molecular sciences · 2021Review
- Identifying a Hypoxia-Related Long Non-Coding RNAs Signature to Improve the Prediction of Prognosis and Immunotherapy Response in Hepatocellular Carcinoma.Frontiers in genetics · 2021Article
- Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes.Frontiers in veterinary science · 2021Article
- Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases.International journal of molecular sciences · 2020Review
- Leptin: an unappreciated key player in SLE.Clinical rheumatology · 2020Review
- Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities.Molecular cancer · 2019Review
- Cigarette Smoking Modulation of Saliva Microbial Composition and Cytokine Levels.International journal of environmental research and public health · 2018Article
- Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adaptive immune response against hepatocellular carcinoma (HCC) could be a therapeutic target to restrain HCC initiation and growth. The interactions between hepatoma cells and immune cells modify the anti-tumor immunity to influence hepatoma cell survival. To explore the potential interplay between hepatoma cells and anti-HCC T-cells, we conducted a HCC induction mouse model to analyze the phenotypic and functional alterations of T-cell subsets. We found that both hepatoma tissues and hepatoma cell lines substantially produced higher leptin, which is an adipokine usually expressed in fat tissue, than normal liver tissue or hepatocytes. We also found that regulatory T-cells (Tregs), effector CD4(+) T-cells and CD8(+) T-cells upregulated expression of leptin receptor (LEPR) in spleens and livers after HCC induction. In vitro study showed that macrophages and dendritic cells isolated from HCC livers upregulated LEPR expression on T-cells. Leptin inhibited Treg activation and function in vitro, demonstrated by lower expression of TGF-β, IL-10, CTLA4 and GITR in Tregs, as wells weaker suppression of CD8(+) T-cell proliferation and production of cytotoxic mediators. In addition, silencing LEPR in Tregs favored tumor growth in a hepatoma cell line allograft model. Taken together, our study suggests that hepatoma cells could enhance anti-HCC immunity through secreting leptin to down-regulate Treg activity and subsequently promote CD8(+) T-cell response.
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