Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer.
Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer.
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DOI：
10.1186/1471-2407-9-231
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发表时间：
2009-07-15
期刊：
影响因子：
3.8
通讯作者：
Leidenius MH
中科院分区：
文献类型：
--
作者：
Mansfield AS;Heikkila PS;Vaara AT;von Smitten KA;Vakkila JM;Leidenius MH
有证据表明，乳腺癌患者的免疫系统功能失调。调节性T细胞（TCLs）和IDO（一种免疫抑制酶）与某些癌症中的更晚期疾病相关，并可能促进对肿瘤的免疫耐受。我们的目的是评估是否表达Foxp 3，一个标志物TGFAP，IDO与乳腺癌患者的淋巴结转移。IDO的抑制剂是可用的，并且如果IDO驱动疾病的进展，则可能在乳腺癌中表现出效用。采用免疫组化法检测47例乳腺癌前哨淋巴结（SLN）Foxp 3和IDO的表达。对阳性染色细胞进行定量，并记录其在SLN内的分布。癌症患者SLN中Foxp 3+细胞的比例高于对照组（19% vs.10%，p < 0.001）。具体地，在具有转移的SLN中比无肿瘤的SLN中存在更多的Foxp 3+细胞（20%对14%，p = 0.02）。癌症患者的SLN中IDO+细胞的比例与对照相比没有统计学差异（4.0%对1.6%，p = 0.08）。为了证明Foxp 3和IDO的联合免疫抑制作用，我们将每个SLN分类为Foxp 3和IDO阳性或阴性。Foxp 3 +/IDO+组几乎完全由具有淋巴结阳性疾病的癌症患者组成。总之，我们的研究表明，Foxp 3+细胞与乳腺癌中更晚期的疾病有关，这一发现在许多其他癌症中被证明是正确的。由于已发现IDO促进T细胞分化，IDO可能成为消除T细胞耐受性的发展并促进对乳腺癌的有效免疫应答的合适靶点。IDO和Foxp 3在SLN中的联合表达支持了这一假设。
There is evidence that the immune systems of patients with breast cancer are dysfunctional. Regulatory T cells (Tregs), and IDO, an immunosuppressive enzyme, are associated with more advanced disease in some cancers and may promote immunologic tolerance to tumors. Our aim was to assess whether expression of Foxp3, a marker of Tregs, and IDO were linked with nodal metastasis in breast cancer patients. Inhibitors of IDO are available and could potentially demonstrate utility in breast cancer if IDO drives progression of disease. Sentinel lymph nodes (SLN) of 47 breast cancer patients with varying degrees of nodal disease and 10 controls were evaluated for expression of Foxp3 and IDO using immunohistochemistry. Positively stained cells were quantified and their distribution within the SLN noted. The proportion of Foxp3+ cells was higher in SLN of cancer patients than controls (19% v. 10%, p < 0.001). Specifically, there were more Foxp3+ cells in SLN with metastasis than tumor-free SLN (20% v. 14%, p = 0.02). The proportion IDO+ cell in SLN of cancer patients was not statistically different than controls (4.0% v. 1.6%, p = 0.08). In order to demonstrate the combined immunosuppressive effect of Foxp3 and IDO, we categorized each SLN as positive or negative for Foxp3 and IDO. The Foxp3+/IDO+ group almost exclusively consisted of cancer patients with node positive disease. In conclusion, our study shows that Foxp3+ cells are associated with more advanced disease in breast cancer, a finding that is proving to be true in many other cancers. As IDO has been found to promote differentiation of Tregs, IDO may become a suitable target to abrogate the development of T-cell tolerance and to promote an effective immune response to breast cancer. Our results about the combined expression of IDO and Foxp3 in metastastic SLN support this assumption.
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影响因子：
8.8
作者：
Polak, M. E.;Borthwick, N. J.;Gabriel, F. G.;Johnson, P.;Higgins, B.;Hurren, J.;McCormick, D.;Jager, M. J.;Cree, I. A.
通讯作者：
Cree, I. A.
影响因子：
11.5
作者：
Brandacher, G;Perathoner, A;Amberger, A
通讯作者：
Amberger, A
影响因子：
11.2
作者：
Hou, De-Yan;Muller, Alexander J.;Munn, David H.
通讯作者：
Munn, David H.
影响因子：
6.2
作者：
Matsuura, K;Yamaguchi, Y;Toge, T
通讯作者：
Toge, T
DOI：
10.1084/jem.189.9.1363
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Munn DH;Shafizadeh E;Attwood JT;Bondarev I;Pashine A;Mellor AL
通讯作者：
Mellor AL