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Open Access 01-12-2012 | Original Article

Effective modulation of CD4⁺CD25^+high regulatory T and NK cells in malignant patients by combination of interferon-α and interleukin-2

Authors: Guangxian Liu, Wuwei Yang, Mei Guo, Xiaoqing Liu, Naixiang Huang, Dingfeng Li, Zefei Jiang, Wenfeng Yang, Weijing Zhang, Hang Su, Zhiqing Liu, Tieqiang Liu, Dongmei Wang, Shan Huang, Bo Yao, Qiuhong Man, Lijuan Qiu, Xuedong Sun, Yuying Sun, Bing Liu

Published in: Cancer Immunology, Immunotherapy | Issue 12/2012

Abstract

Overinduced CD4⁺CD25^+high regulatory T cells (Treg) and downregulated NK cells contribute to tumor-relevant immune tolerance and interfere with tumor immunity. In this study, we aimed to design a novel strategy with cytokine combination to correct the dysregulated Treg and NK cells in malignant patients. Initially, a total of 58 healthy individuals and 561 malignant patients were analyzed for their cellular immunity by flow cytometry. The average percentages of CD4⁺CD25^+high/lymphocyte were 1.30 ± 1.19 % (\( \bar{x} \) ± SD) in normal adults and 3.274 ± 4.835 % in malignant patients (p < 0.001). The ratio of CD4⁺CD25^+high to CD4⁺ was 3.58 ± 3.19 % in normal adults and 6.01 ± 5.89 % to 13.50 ± 23.60 % in different kinds of malignancies (p < 0.001). Of normal adults, 15.52 % had >3 % Treg and 12.07 % had <10 % NK cells. In contrast, the Treg (>3 %) and NK (<10 %) percentages were 40.82 and 34.94 % in malignant patients, respectively. One hundred and ten patients received the immunomodulation therapy with IFN-α and/or IL-2. The overinduced Treg in 86.3 % and the reduced NK cells in 71.17 % of the patients were successfully modulated. In comparison, other lymphocyte subpopulations in most patients were much less affected by this treatment. No other treatment-relevant complications except slight pyrexia, fatigue, headache, and myalgia were observed. In conclusion, dysregulated Treg and/or NK cells were common in malignant patients. Different from any regimens ever reported, this strategy was simple and effective without severe complications and will become a basic regimen for other cancer therapies.

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Title: Effective modulation of CD4+CD25+high regulatory T and NK cells in malignant patients by combination of interferon-α and interleukin-2
Authors: Guangxian Liu
Wuwei Yang
Mei Guo
Xiaoqing Liu
Naixiang Huang
Dingfeng Li
Zefei Jiang
Wenfeng Yang
Weijing Zhang
Hang Su
Zhiqing Liu
Tieqiang Liu
Dongmei Wang
Shan Huang
Bo Yao
Qiuhong Man
Lijuan Qiu
Xuedong Sun
Yuying Sun
Bing Liu
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 12/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-012-1297-2

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