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

Springer Science and Business Media LLC - Tập 61 - Trang 2357-2366 - 2012
Guangxian Liu1, Wuwei Yang2, Mei Guo1, Xiaoqing Liu2, Naixiang Huang2, Dingfeng Li2, Zefei Jiang2, Wenfeng Yang2, Weijing Zhang2, Hang Su2, Zhiqing Liu1, Tieqiang Liu1, Dongmei Wang1, Shan Huang1, Bo Yao1, Qiuhong Man1, Lijuan Qiu1, Xuedong Sun1, Yuying Sun2, Bing Liu2
1Department of Hematology and Transplantation, Affiliated Hospital of the Academy of Military Medical Sciences, Beijing, China
2Cancer Therapy Center, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China

Tóm tắt

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.

Tài liệu tham khảo

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