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A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4+CD25+Foxp3+ T Cells
Open accessAbstract
Background & aims Several studies have shown that development of hepatocellular carcinoma (HCC) generates a number of immune suppressive mechanisms in these patients. Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that have been shown to inhibit T-cell responses in tumor-bearing mice, but little is known about these cells in humans owing to a lack of specific markers. In this study, we have investigated the frequency and function of a new population of MDSC denoted here as CD14(+)HLA-DR(-/low) in HCC patients. We have also identified a novel, MDSC-mediated immune regulatory pathway in these patients.Methods We have directly isolated and characterized MDSCs for phenotype and function from peripheral blood (n = 111) and tumor (n = 12) of patients with HCC.Results The frequency of CD14(+)HLA-DR(-/low) cells in peripheral blood mononuclear cells (PBMC) from HCC patients was significantly increased in comparison with healthy controls. CD14(+) HLA-DR(-/low) cells were unable to stimulate an allogeneic T-cell response, suppressed autologous T-cell proliferation, and had high arginase activity, a hallmark characteristic of MDSC. Most important, CD14(+)HLA-DR(-/low) cells from HCC patients induced a CD4(+)CD25(+)Foxp3(+) regulatory T-cell population when cocultured with autologous T cells.Conclusion CD14(+)HLA-DR(-/low) cells are a new population of MDSC increased in blood and tumor of HCC patients. We propose a new mechanism by which MDSC exert their immunosuppressive function, through the induction of CD4(+)CD25(+)Foxp3(+) regulatory T cells in cocultured CD4(+) T cells. Understanding the mechanism of action of MDSC in HCC patients is important in the design of effective immunotherapeutic protocols.
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“The liver also contains an abundance of MDSCs that produce factors suppressing T cell activation63.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [63]
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Metadata
- Authors
- Hoechst, B., Ormandy, L. A., Ballmaier, M., Lehner, F., Krüger, C., Manns, M. P., Greten, T. F., & Korangy, F.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Korangy, Firouzeh
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 135
- Issue
- 1
- Pages
- 234-243
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2059688175
- Cited by
- 793
- References
- 31
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 25 · 2023: 34 · 2022: 50 · 2021: 46 · 2020: 53 · 2019: 40 · 2018: 39 · 2017: 60 · 2016: 54 · 2015: 65 · 2014: 55 · 2013: 65 · 2012: 59
- FWCI
- 15.02
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-08-01)
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB-738)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- myeloid-derived suppressor cells, hepatocellular carcinoma, regulatory T cells, immunosuppression, arginase activity, CD4+CD25+Foxp3+ T cells, tumor immune microenvironment, T cell proliferation inhibition, cancer immunotherapy
- MeSH terms
- Aged, Arginase, Cell Communication, Cell Division, Cells, Cultured, Female, Flow Cytometry, Carcinoma, Hepatocellular, HLA-DR Antigens, Humans, Immune Tolerance, Liver Neoplasms, Male, Middle Aged, Biomarkers, CD4-Positive T-Lymphocytes, CD4 Antigens, Immunophenotyping, Interleukin-10, Lipopolysaccharide Receptors, Myeloid Cells, Forkhead Transcription Factors, Interleukin-2 Receptor alpha Subunit
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