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 +/- A 1.19 % ( +/- A SD) in normal adults and 3.274 +/- A 4.835 % in malignant patients (p < 0.001). The ratio of CD4(+)CD25(+high) to CD4(+) was 3.58 +/- A 3.19 % in normal adults and 6.01 +/- A 5.89 % to 13.50 +/- A 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-alpha 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.