First Department of Surgery, University of Yamanashi, Chuo City, Yamanashi, Japan.
Dis Esophagus. 2010 Jul;23(5):422-9. doi: 10.1111/j.1442-2050.2009.01029.x. Epub 2009 Dec 11.
It has been reported that an increased population of regulatory T cells (T-regs) is one of the reasons for impaired anti-tumor immunity. We investigated the frequency of Foxp3(+) T-regs in tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) of patients with esophageal squamous cell carcinoma (ESCC). Furthermore, in order to elucidate the mechanisms behind T-regs accumulation within tumors, we evaluated the relationship between CCL17 or CCL22 expression and the frequency of Foxp3(+) T-regs. CD4(+)CD25(+)Foxp3(+) T-regs as a percentage of CD4(+) cells were counted by flow cytometry. The frequency of CCL17(+) or CCL22(+) cells among CD14(+) cells in tumors was also evaluated by flow cytometry. Moreover, an in vitro migration assay using T-regs derived from ESCC was performed in the presence of CCL17 or CCL22. The frequency of Foxp3(+) T-regs in TILs was significantly higher than that in the normal esophageal mucosa (24.6 +/- 10.0 vs 7.1 +/- 5.9%, P < 0.01). The frequency of Foxp3(+) T-regs in PBLs of ESCC patients was significantly higher than that in normal healthy donors (7.0 +/- 4.2 vs 2.5 +/- 1.0%, P < 0.01). Furthermore, the frequency of CCL17(+) or CCL22(+) cells among CD14(+) cells within tumors was significantly higher than that of normal esophageal mucosa, and there was a significant correlation between the frequency of CCL17(+) or CCL22(+) cells and Foxp3(+) T-regs in TILs. In addition, the in vitro migration assay indicated that T-regs were significantly induced to migrate by CCL17 or CCL22. In conclusion, CCL17 and CCL22 within the tumor are related to the increased population of Foxp3(+) T-regs in ESCC.
据报道，调节性 T 细胞（T-regs）的增加是抗肿瘤免疫受损的原因之一。我们研究了食管鳞状细胞癌（ESCC）患者肿瘤浸润淋巴细胞（TILs）和外周血淋巴细胞（PBLs）中 Foxp3+T-regs 的频率。此外，为了阐明肿瘤内 T-regs 积累的机制，我们评估了 CCL17 或 CCL22 表达与 Foxp3+T-regs 频率之间的关系。通过流式细胞术计数 CD4+CD25+Foxp3+T-regs 占 CD4+细胞的百分比。通过流式细胞术还评估了肿瘤中 CD14+细胞中 CCL17+或 CCL22+细胞的频率。此外，在 CCL17 或 CCL22 存在的情况下，对来自 ESCC 的 T-regs 进行了体外迁移测定。TILs 中 Foxp3+T-regs 的频率明显高于正常食管黏膜（24.6±10.0%比 7.1±5.9%，P<0.01）。ESCC 患者 PBLs 中 Foxp3+T-regs 的频率明显高于正常健康供体（7.0±4.2%比 2.5±1.0%，P<0.01）。此外，肿瘤内 CD14+细胞中 CCL17+或 CCL22+细胞的频率明显高于正常食管黏膜，并且 TILs 中 CCL17+或 CCL22+细胞的频率与 Foxp3+T-regs 之间存在显著相关性。此外，体外迁移测定表明 CCL17 或 CCL22 可显著诱导 T-regs 迁移。总之，肿瘤内的 CCL17 和 CCL22 与 ESCC 中 Foxp3+T-regs 的增加有关。
