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Effective modulation of CD4(+)CD25 (+high) regulatory T and NK cells in malignant patients by combination of interferon-? and interleukin-2.


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 % ([Formula: see text] ± 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-? 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.

SUBMITTER: Liu G 

PROVIDER: S-EPMC3506201 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Liu Guangxian G   Yang Wuwei W   Guo Mei M   Liu Xiaoqing X   Huang Naixiang N   Li Dingfeng D   Jiang Zefei Z   Yang Wenfeng W   Zhang Weijing W   Su Hang H   Liu Zhiqing Z   Liu Tieqiang T   Wang Dongmei D   Huang Shan S   Yao Bo B   Man Qiuhong Q   Qiu Lijuan L   Sun Xuedong X   Sun Yuying Y   Liu Bing B  

Cancer immunology, immunotherapy : CII 20120622 12


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 w  ...[more]

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