CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers
CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers
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DOI：
10.1007/s00262-005-0092-8
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发表时间：
2006-09-01
影响因子：
5.8
通讯作者：
Fujii, Hideki
中科院分区：
文献类型：
--
作者：
Kono, Koji;Kawaida, Hiromichi;Fujii, Hideki
目的：调节性T细胞（Regulatory T cells，T细胞）可抑制T细胞介导的免疫应答。已经表明，在几种不同的人类恶性肿瘤中，T β的比例增加，尽管实际机制仍不清楚。在本研究中，我们评估了胃癌和食管癌患者PBMC中CD 4（+）CD 25（高）T细胞的患病率与临床结局的关系。研究方法：采用流式细胞术三色染色法检测72例胃癌和42例食管癌患者外周血单个核细胞（PBMC）中CD 4（+）CD 25（high）T细胞占总CD 4（+）细胞的比例。采用Kaplan-Meier法分析患者的精算总生存率。结果如下：胃癌和食管癌患者CD 4 + CD 25（high）T细胞百分率分别为4.9 ± 1.2%和5.2 ± 2.1%，明显高于健康人（1.9 ± 1.1%，P < 0.01）。CD 4（+）CD 25（high）T细胞在胃癌和食管癌中的分布在早期和晚期之间有显著性差异（I期与III期比较，P <0.05; I期与IV期比较，P < 0.05）。在胃癌和食管癌中，CD 4（+）CD 25（高）T细胞比例高的患者与比例低的患者相比，生存率较差。57例胃癌患者手术切除后，CD 4 + CD 25（high）T细胞比例明显降低，与正常人接近。此外，对术后复发肿瘤的胃癌患者（n=6）的研究显示，与术后2个月相比，CD 4（+）CD 25（高）T细胞的患病率单独增加。CD 4（+）CD 25（high）T细胞表达FOXP 3 mRNA，并具有丰富的CD 45 RO和细胞内CTLA-4分子。结论：肿瘤相关因素诱导并扩增了CD 4（+）CD 25（high）T细胞。
Purpose: Regulatory T cells (T regs) can inhibit immune responses mediated by T cells. It has been shown that there is an increased proportion of T regs in several different human malignancies, although the actual mechanism remains unclear. In the present study, we evaluated the prevalence of CD4(+)CD25(high) T regs in PBMCs from patients with gastric and esophageal cancers in relation to the clinical outcome. Methods: PBMCs in 72 patients with gastric cancer and 42 patients with esophageal cancer were evaluated for the proportion of CD4(+)CD25(high) T cells, as a percentage of the total CD4(+) cells, by flow cytometric analysis with triple-color staining. Actuarial overall survival rates of the patients were analyzed by the Kaplan-Meier method. Results: The percentages of CD4(+)CD25(high) T cells for cases of gastric cancer (4.9 +/- 1.2%) and esophageal cancer (5.2 +/- 2.1%) were significantly higher than those for healthy donors (1.9 +/- 1.1%, P < 0.01). There were significant differences in the prevalence of CD4(+)CD25(high) T cells between the early and advanced disease stages, both in gastric cancer (stage I vs. III, P < 0.05; stage I vs. IV, P < 0.05) and esophageal cancer (stage I vs. IV, P < 0.05). The patients with a high proportion of CD4(+)CD25(high) T cells showed poorer survival rates in comparison to those with a low proportion, in both gastric and esophageal cancers. After patients received curative resections of gastric cancers (n=57), the increased proportions of CD4(+)CD25(high) T cells were significantly reduced, and the levels were almost equal to those in normal healthy donors. In addition, studies of gastric cancer patients with postoperative recurrent tumors (n=6) revealed that the prevalence of CD4(+)CD25(high) T cells individually increased compared to 2 months after the operations. CD4(+)CD25(high) T cells expressed FOXP3 mRNA and had abundant CD45RO and intracellular CTLA-4 molecules. Conclusions: These results strongly suggest that tumor-related factors induce and expand CD4(+)CD25(high) T regs.