Laboratory for Immunological and Molecular Cancer Research, Third Medical Department With Hematology, Medical Oncology, Hemostaseology, Rheumatology, and Infectious Disease of the Private Medical University Hospital of Salzburg, Salzburg, Austria.
Cancer. 2011 May 15;117(10):2163-9. doi: 10.1002/cncr.25752. Epub 2010 Nov 18.
Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression.
T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data.
The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028).
Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia.
早期慢性淋巴细胞白血病的病程具有高度可变性。由于调节性 T 细胞(Treg)是抗肿瘤免疫的强大抑制剂,作者假设 Treg 的增加可能有利于疾病进展。
通过流式细胞术分析 102 例患者外周血中的 Treg 水平(CD3 阳性、CD4 阳性、CD25 阳性和 CD127 阴性)。采用统计学分析评估与临床数据的相关性。
与 170 名健康对照个体相比,慢性淋巴细胞白血病患者 CD4 阳性 T 细胞中的相对 Treg 数量明显更高(P =.001)。使用中位数 Treg 值 9.7%(CD4 阳性 T 细胞的百分比)将患者分为 2 组。与 Treg 水平较低的患者(中位时间 11.7 年;对数秩检验 P =.019)相比,Treg 水平较高的患者初始治疗时间明显更短(中位时间 5.9 年)。此外,在单变量分析中(P =.023)和包括 Rai 分期、免疫球蛋白重链可变区基因突变状态、染色体异常和 CD38 表达的多变量 Cox 回归分析中(P =.028),Treg 水平(CD4 阳性 T 细胞的百分比)对预测初始治疗时间具有显著的预后价值。
在低至中危期慢性淋巴细胞白血病患者中,较高的 Treg 水平对预测初始治疗时间具有显著且独立的预后价值。