Cited by 793Immune cells in cancerImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

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A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4+CD25+Foxp3+ T Cells

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Hoechst, Bastian, Ormandy, Lars A., Ballmaier, Matthias, Lehner, Frank, Krüger, Christine, Manns, Michael P., Greten, Tim F., Korangy, Firouzeh·2008·Gastroenterology

DOI 10.1053/j.gastro.2008.03.020

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Abstract

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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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
ORCID: Ballmaier, Matthias
Lehner, Frank
Manns, Michael P.
Greten, Tim F.
Korangy, Firouzeh
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2008-07
Volume: 135
Issue: 1
Pages: 234-243
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2008.03.020
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4+CD25+Foxp3+ T Cells

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