Department of Hematology and Transplantation, Affiliated Hospital of the Academy of Military Medical Sciences, Dongdajie 8, Beijing, 100071, China.
Cancer Immunol Immunother. 2012 Dec;61(12):2357-66. doi: 10.1007/s00262-012-1297-2. Epub 2012 Jun 22.
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.
过诱导的 CD4(+)CD25(+high)调节性 T 细胞（Treg）和下调的 NK 细胞导致与肿瘤相关的免疫耐受，并干扰肿瘤免疫。在这项研究中，我们旨在设计一种新的细胞因子联合策略来纠正恶性患者中失调的 Treg 和 NK 细胞。最初，通过流式细胞术分析了 58 名健康个体和 561 名恶性患者的细胞免疫。正常成年人的 CD4(+)CD25(+high)/淋巴细胞平均百分比为 1.30±1.19%（[公式：见正文]±SD），恶性患者为 3.274±4.835%（p<0.001）。正常成年人的 CD4(+)CD25(+high)与 CD4(+)的比值为 3.58±3.19%，而不同类型恶性肿瘤为 6.01±5.89%至 13.50±23.60%（p<0.001）。在正常成年人中，有 15.52%的人 Treg>3%，有 12.07%的人 NK 细胞<10%。相比之下，恶性患者中 Treg（>3%）和 NK（<10%）的百分比分别为 40.82%和 34.94%。110 名患者接受 IFN-α和/或 IL-2 的免疫调节治疗。在 86.3%的患者中，过诱导的 Treg 和在 71.17%的患者中降低的 NK 细胞成功地被调节。相比之下，大多数患者的其他淋巴细胞亚群受这种治疗的影响较小。除了轻微发热、疲劳、头痛和肌痛外，未观察到其他与治疗相关的并发症。总之，恶性患者中存在失调的 Treg 和/或 NK 细胞。与以往任何报道的方案不同，该方案简单有效，无严重并发症，将成为其他癌症治疗的基本方案。
