Effective modulation of CD4(+)CD25          (+high) regulatory T and NK cells in malignant patients by combination of interferon-α and interleukin-2.
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-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.
Department of Hematology and Transplantation, Affiliated Hospital of the Academy of Military Medical Sciences, Dongdajie 8, Beijing, 100071, China. liugx270@hotmail.com
Guangxian
G
Liu
Wuwei
W
Yang
Mei
M
Guo
Xiaoqing
X
Liu
Naixiang
N
Huang
Dingfeng
D
Li
Zefei
Z
Jiang
Wenfeng
W
Yang
Weijing
W
Zhang
Hang
H
Su
Zhiqing
Z
Liu
Tieqiang
T
Liu
Dongmei
D
Wang
Shan
S
Huang
Bo
B
Yao
Qiuhong
Q
Man
Lijuan
L
Qiu
Xuedong
X
Sun
Yuying
Y
Sun
Bing
B
Liu
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056747:Immunomodulation / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C508017:IL2RA protein, human; D016898:Interferon-alpha; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit