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Increased Frequency of CD4+CD25highFoxP3+ Regulatory T Cells in Patients with Hepatocellular Carcinoma

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Accumulating evidence suggests regulatory T cells (Tregs) are associated with impaired antitumor responses. However, the relationship between the CD4+CD25highFoxP3+ Treg and hepatocellular carcinoma (HCC) has not been well investigated. Levels of CD4+CD25highFoxP3+ Tregs in peripheral blood mononuclear cells (PBMCs) from HCC patients and healthy donors, tumor infiltrating lymphocytes (TILs) extracted from HCC, and hepatic lymphocytes extracted from resected liver were measured by flow cytometry, and their effects on T-cell proliferation was determined by 3H-thymidine incorporation. Serum levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 were measured by enzyme linked immunosorbent assay. The frequency of Tregs in PBMCs from HCC patients was higher than that from healthy donors. Similarly, the frequency of Tregs in TILs was higher than that of hepatic lymphocytes. On the other hand, the 3H-thymidine uptake by TILs and PBMCs from HCC patients was decreased drastically when compared to the counterparts from normal controls. Furthermore, serum IL-10 and TGF-β1 levels increased significantly in HCC patients when compared to the healthy donors. This study identified an increased frequency of CD4+CD25highFoxP3+ Tregs in patients with HCC. The elevated serum IL-10, TGF-β1 levels also correlated with impaired antitumor responses in these patients. Further effort is needed to establish new immunotherapeutic strategies designed to modulate Tregs to promote a competent antitumor response.

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Abbreviations

Treg:

Regulatory T cell

HCC:

Hepatocellular carcinoma

TIL:

Tumor infiltrating lymphocyte

PBMC:

Peripheral blood mononuclear cell

PHA:

Phytohaemagglutinin

TGF:

Transforming growth factor

IL:

Interleukin

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Acknowledgments

This research was supported by grant from the Science and Technology Department of Sichuan Province, People’s Republic of China.

Conflict of interest

All the authors who have taken part in this study declared they have nothing to disclose regarding competing interests or funding from industry with respect to this manuscript.

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Authors and Affiliations

  1. Department of General Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan Province, China

    Xi Feng, Bo Li, Hui Ye & Dan Long

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  1. Xi Feng
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  2. Bo Li
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  3. Hui Ye
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  4. Dan Long
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Correspondence to Hui Ye.

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Feng, X., Li, B., Ye, H. et al. Increased Frequency of CD4+CD25highFoxP3+ Regulatory T Cells in Patients with Hepatocellular Carcinoma. Arch. Immunol. Ther. Exp. 59, 309–314 (2011). https://doi.org/10.1007/s00005-011-0127-0

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  • DOI: https://doi.org/10.1007/s00005-011-0127-0

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