肿瘤负荷对大肠癌患者外周血T细胞分化的影响

目的 探讨肿瘤负荷对于大肠癌患者外周血T1（分泌Ⅰ类因子T细胞）、T2（分泌Ⅱ类因子T细胞）分化的影响及其临床意义。方法 连续采集20例大肠癌患者（17例行根治术、3例行姑息切除术）初诊时及去除瘤负荷后第7天外周血,同期年龄、性别匹配的20例良性疾病患者外周血作为对照。应用胞内因子检测法检测T1、T2;应用流式细胞术检测淋巴细胞亚群（T、CD4^＋T、CD8^＋T、B、NK）。结果 大肠癌患者外周血T1、12明显低于对照组（P=0．006,0．017）;淋巴细胞亚群无明显改变。去除肿瘤负荷后7dT1升高（P〉0．05）,T2明显升高（P=O．020）。肿瘤直径≥5cm及低分化癌患者的T1分别低于肿瘤直径〈5cm及高、中分化癌患者（P=0．064,0．072）;有淋巴结转移患者的T1明显低于无淋巴结转移患者（P=0．033）;Ⅲ＋Ⅳ期患者的T1明显低于Ⅰ＋Ⅱ期患者（P=0．033）。结论肿瘤负荷可以显著抑制大肠癌患者外周血T1、12的分化,这是导致机体抗肿瘤免疫功能低下的机制之一;去除肿瘤负荷后短时间内T1、12即开始升高,免疫功能得到一定的改善;T1可能是一种新的大肠癌预后指标。

Effect of tumor burden on differentiation of T lymphocytes in the peripheral blood of patients with colorectal cancer

OBJECTIVE: To analyze the effect of tumor burden on the differentiation of T1 and T2 cells and its implication in patients with colorectal cancer. METHODS: Peripheral venous blood samples were obtained from 20 patients with primary colorectal cancer before and 7 days after the operation, radical operation in 17 patients and palliative resection in 3 patients. Twenty sex and age-matched patients with benign diseases treated in the same period were used as controls. T1 and T2 cells in the peripheral blood were evaluated by detecting the intracellular interferon-gamma and interleukin-4 production with 4-color flow cytometry. Lymphocyte subsets in the peripheral blood were also measured by flow cytometry. RESULTS: At the time of diagnosis, the percentage of T1 and T2 cells in the peripheral lymphocytes of the case group was lower significantly than that of the control group (P = 0.006, and P = 0.017). There was no significant difference in the T, CD4(+) T, CD8(+) T, B, and NK cells between the two groups. After getting rid of the tumor burden, the percentage of T1 cells increased, however, not significantly (P > 0.05). And the percentage of T2 cells increased significantly (P = 0.020). The percentages of T1 cell of the patients with the tumor > or = 5 cm and of the patients with poorly differentiated tumors were significantly lower than those of the patients with the tumor < 5 cm and of the patients with well or moderately differentiated tumors (P = 0.064, and P = 0.072). The percentage of T1 cells in the patients with lymph node metastasis and stage III approximately IV tumor were lower significantly than those of the patients without lymph node metastasis and those with stage I approximately II tumor (P = 0.033 and P = 0.033). No significant differences were found between the population of T1 cells and such factors as tumor size, serosa invasion, and distant metastasis. CONCLUSION: Tumor load suppresses the differentiation of T1 and T2 cells in the patients with colorectal cancer significantly, and may be an important factor in the development of immunosuppression. After getting rid of the tumor burden, the percentages of T1 and T2 increase in a short time, and the immunologic function is improved. Determination of T1 may be helpful to indicate the prognosis of colorectal cancer.