Suppression of tumour-specific CD4⁺ T cells by regulatory T cells is associated with progression of human colorectal cancer.
Suppression of tumour-specific CD4⁺ T cells by regulatory T cells is associated with progression of human colorectal cancer.
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DOI：
10.1136/gutjnl-2011-300970
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发表时间：
2012-08
期刊：
影响因子：
24.5
通讯作者：
Godkin A
中科院分区：
文献类型：
--
作者：
Betts G;Jones E;Junaid S;El-Shanawany T;Scurr M;Mizen P;Kumar M;Jones S;Rees B;Williams G;Gallimore A;Godkin A
有间接证据表明，T细胞反应可以控制结直肠癌（CRC）的转移扩散。然而，CD4+Foxp3+调节性T细胞（Tregs）的富集也有文献记载。评估结直肠癌是否促进Treg活性及其如何影响抗肿瘤免疫反应和疾病进展。在肿瘤切除前后对一组患者进行了Treg活性的纵向研究。同时检测CD4+ T细胞对肿瘤相关抗原癌胚抗原（CEA）和5T4的特异性反应。与年龄匹配的健康对照相比，62例术前结直肠癌患者的treg表达Foxp3水平显著升高（p=0.007），术后恢复正常（p=0.0075）。在大约三分之二的患者中观察到CD4+ T细胞对一种或两种肿瘤相关抗原（CEA和5T4）的反应，其中三分之一的反应被Tregs抑制。引人注目的是，在所有12个月肿瘤复发的患者中，术前观察到明显的肿瘤特异性抑制（p=0.003），但没有控制CD4+ T细胞反应。这些发现表明，CRC的存在驱动Tregs的活性，并伴随抑制CD4+ T细胞对肿瘤相关抗原的反应。抑制与12个月肿瘤复发相关，这意味着Tregs有助于疾病进展。这些发现为操纵Tregs进行治疗干预提供了理论依据。
There is indirect evidence that T cell responses can control the metastatic spread of colorectal cancer (CRC). However, an enrichment of CD4+Foxp3+ regulatory T cells (Tregs) has also been documented. To evaluate whether CRC promotes Treg activity and how this influences anti-tumour immune responses and disease progression. A longitudinal study of Treg activity on a cohort of patients was performed before and after tumour resection. Specific CD4+ T cell responses were also measured to the tumour associated antigens carcinoembryonic antigen (CEA) and 5T4. Tregs from 62 preoperative CRC patients expressed a highly significant increase in levels of Foxp3 compared to healthy age-matched controls (p=0.007), which returned to normal after surgery (p=0.0075). CD4+ T cell responses to one or both of the tumour associated antigens, CEA and 5T4, were observed in approximately two-thirds of patients and one third of these responses were suppressed by Tregs. Strikingly, in all patients with tumour recurrence at 12 months, significant preoperative suppression was observed of tumour-specific (p=0.003) but not control CD4+ T cell responses. These findings demonstrate that the presence of CRC drives the activity of Tregs and accompanying suppression of CD4+ T cell responses to tumour-associated antigens. Suppression is associated with recurrence of tumour at 12 months, implying that Tregs contribute to disease progression. These findings offer a rationale for the manipulation of Tregs for therapeutic intervention.
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影响因子：
11.2
作者：
Ambrosino, Elena;Spadaro, Michela;Cavallo, Federica
通讯作者：
Cavallo, Federica
DOI：
10.1073/pnas.192162899
发表时间：
2002-10-01
影响因子：
11.1
作者：
Lehmann, J;Huehn, J;Hamann, A
通讯作者：
Hamann, A
影响因子：
45.3
作者：
Salama, Paul;Phillips, Michael;Iacopetta, Barry
通讯作者：
Iacopetta, Barry
影响因子：
6.4
作者：
HOLE, N;STERN, PL
通讯作者：
STERN, PL
影响因子：
4.4
作者：
Oo, Ye H.;Weston, Chris J.;Adams, David H.
通讯作者：
Adams, David H.