Shen Li-Song, Wang Jian, Shen Ding-Feng, Yuan Xiang-Liang, Dong Ping, Li Mei-Xing, Xue Jian, Zhang Feng-Min, Ge Hai-Liang, Xu Dakang
Department of Clinical Laboratory, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Clin Immunol. 2009 Apr;131(1):109-18. doi: 10.1016/j.clim.2008.11.010. Epub 2009 Jan 18.
Increased populations of regulatory T cells (Tregs) impair anti-tumor immunity. Recently, the transcription factor Foxp3 has been reported to play a key role in CD4(+)CD25(+) regulatory T cell function and represents a specific marker for these cells. However, Foxp3 is a nuclear protein and is of limited value in the isolation of Tregs, which is a major reason that many functionally relevant aspects of Treg cells are still unknown. Here, we have characterized CD4(+)CD25(+)CD127(low/)- as the surface marker of regulatory T cells in gastric cancer. 88.1-96.1%of CD25(+)CD127(low/-) T cells expressed Foxp3, the frequency of CD4(+)CD25(+)CD127(low/-) regulatory T cells in the peripheral blood of gastric cancer patients was significantly higher than that in healthy controls. Increased CD4(+)CD25(+)CD127(low/-) regulatory T cells were also present in the tumor microenvironment, such as those found in the ascites fluid, tumor tissue or adjacent lymph nodes. Particularly those Treg cells associated with the TNM stage. In addition, we found that CD4(+)CD25(+)CD127(low/-) Tregs suppressed effector T cell proliferation and also correlated to advanced stage of gastric cancer. Thus, CD4(+)CD25(+)CD127(low/-) can be used as a selective biomarker to enrich human Treg cells and also to perform functional in vitro assays in gastric cancer.
调节性T细胞(Tregs)数量增加会损害抗肿瘤免疫。最近,据报道转录因子Foxp3在CD4(+)CD25(+)调节性T细胞功能中起关键作用,并且是这些细胞的特异性标志物。然而,Foxp3是一种核蛋白,在Tregs的分离中价值有限,这是Treg细胞许多功能相关方面仍不清楚的主要原因。在此,我们已将CD4(+)CD25(+)CD127(low/ -)鉴定为胃癌中调节性T细胞的表面标志物。88.1 - 96.1%的CD25(+)CD127(low/ -) T细胞表达Foxp3,胃癌患者外周血中CD4(+)CD25(+)CD127(low/ -)调节性T细胞的频率显著高于健康对照。肿瘤微环境中也存在CD4(+)CD25(+)CD127(low/ -)调节性T细胞数量增加的情况,如在腹水、肿瘤组织或邻近淋巴结中发现的那样。特别是那些与TNM分期相关的Treg细胞。此外,我们发现CD4(+)CD25(+)CD127(low/ -) Tregs抑制效应T细胞增殖,并且也与胃癌的晚期相关。因此,CD4(+)CD25(+)CD127(low/ -)可作为一种选择性生物标志物,用于富集人Treg细胞,并在胃癌中进行体外功能测定。