CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
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DOI：
10.1371/journal.pone.0000129
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发表时间：
2006-12-27
期刊：
影响因子：
3.7
通讯作者：
Godkin AJ
中科院分区：
文献类型：
--
作者：
Clarke SL;Betts GJ;Plant A;Wright KL;El-Shanawany TM;Harrop R;Torkington J;Rees BI;Williams GT;Gallimore AM;Godkin AJ
利用小鼠模型获得的大量证据表明，CD4+CD25+FOXP3+调节性T细胞(Treg)维持对自身抗原的外周耐受，并抑制抗肿瘤免疫反应。到目前为止，关于结直肠癌(CRC)患者的CD4+T细胞反应的信息有限。我们开始测量T细胞对肿瘤相关抗原的反应，并检查Treg是否影响了CRC患者的抗肿瘤免疫反应。用流式细胞仪鉴定并鉴定Treg细胞为CD4+CD25+FOXP3+。与健康对照组和炎症性肠病(IBD)患者相比，结直肠癌(CRC)患者外周血和肠系膜淋巴结中Treg的表达频率均升高。肿瘤相关抗原5T4的干扰素γ释放法显示，结直肠癌患者外周血单个核细胞(PBMC)中Treg的去除暴露了对肿瘤相关抗原5T4的CD_4~+T细胞反应，而在年龄匹配的健康对照组中没有观察到任何影响。总而言之，这些数据表明，能够抑制肿瘤相关抗原特异性免疫反应的Treg在结直肠癌患者中得到丰富。这些结果支持了操纵Treg来加强癌症免疫治疗的理论基础。
A wealth of evidence obtained using mouse models indicates that CD4+CD25+FOXP3+ regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4+ T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients. Treg were identified and characterized as CD4+CD25+FOXP3+ using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4+ T cell responses, as observed by IFNγ release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group. Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy.
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DOI：
10.1084/jem.193.11.1303
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者：
Schuler G
影响因子：
8.8
作者：
Starzynska, T;Rahi, V;Stern, P L
通讯作者：
Stern, P L
影响因子：
8.8
作者：
HOLE, N;STERN, PL
通讯作者：
STERN, PL
影响因子：
4.4
作者：
Huber, S;Schramm, C;Blessing, M
通讯作者：
Blessing, M
影响因子：
4.4
作者：
Wang, HY;Peng, GY;Wang, RF
通讯作者：
Wang, RF