Special Requirement Ward, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Chin Med J (Engl). 2012 Jun;125(11):2004-11.
Immunosuppressive regulatory T cells (Tregs) participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 (FoxP3) in the aging process and its relationship with lung tumors in humans and mice.
The percentage of CD4(+)CD25(+)CD127(low) Tregs and expression of FoxP3 mRNA were analyzed using flow cytometry (FCM) and real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). Markers were analyzed in the peripheral blood (PB) of 65 elderly patients (age ≥ 65 years) with primary non-small cell lung cancer (NSCLC), 20 younger patients (aged < 55 years) with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, an elderly healthy group, a young tumor group, a middle-aged tumor group, and an elderly tumor group. The percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups.
The percentage of peripheral CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis (TNM) staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice.
The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.
免疫抑制调节性 T 细胞（Tregs）参与肿瘤免疫逃逸，Tregs 的数量和抑制功能随衰老过程而变化，但尚不清楚这种变化是否会导致老年人肿瘤发病率升高。为此，我们设计实验探讨 Tregs 及其功能基因叉头框 P3（FoxP3）在衰老过程中的变化及其与人类和小鼠肺部肿瘤的关系。
采用流式细胞术（FCM）和实时荧光定量聚合酶链反应（FQ-PCR）分析 CD4(+)CD25(+)CD127(low)Tregs 的百分比和 FoxP3 mRNA 的表达。分析了 65 例老年原发性非小细胞肺癌（NSCLC）患者（年龄≥65 岁）、20 例年轻 NSCLC 患者（年龄<55 岁）、30 例老年健康人和 30 例年轻健康人的外周血（PB）标志物。此外，我们建立了 C57BL/6 雌性小鼠的 Lewis 肺癌模型。36 只小鼠分为年轻健康组、中年健康组、老年健康组、年轻肿瘤组、中年肿瘤组和老年肿瘤组。检测六组脾细胞 CD4(+)CD25(+)FoxP3(+)Tregs 的百分比和 FoxP3mRNA 的表达水平。
与其他组相比，老年 NSCLC 患者外周血 CD4(+)CD25(+)CD127(low)Tregs 的百分比和 FoxP3mRNA 的表达明显升高，与年轻健康者相比，老年健康者也明显升高。进一步分析表明，老年 NSCLC 患者外周血 CD4(+)CD25(+)CD127(low)Tregs 的百分比和 FoxP3mRNA 的表达与 TNM 分期密切相关。在小鼠模型中，肿瘤组脾细胞 CD4(+)CD25(+)FoxP3(+)Tregs 的百分比和 FoxP3mRNA 的表达明显高于健康组，其中老年肿瘤组最高。在健康组中，老年健康小鼠的 Tregs 比例和 FoxP3mRNA 的表达最高。老年小鼠的肿瘤比年轻和中年小鼠更大、更重。
随着年龄的增长，Tregs 和 FoxP3 基因的上调可能在老年人群肺癌的发生和发展中发挥重要作用。
