Altered local and systemic immune profiles underlie lymph node metastasis in breast cancer patients.
Altered local and systemic immune profiles underlie lymph node metastasis in breast cancer patients.
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DOI：
10.1002/ijc.27933
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发表时间：
2013-06-01
影响因子：
6.4
通讯作者：
Lee, Peter P.
中科院分区：
文献类型：
--
作者：
Zuckerman, Neta S.;Yu, HongXiang;Simons, Diana L.;Bhattacharya, Nupur;Carcamo-Cavazos, Valeria;Yan, Ning;Dirbas, Frederick M.;Johnson, Denise L.;Schwartz, Erich J.;Lee, Peter P.
癌症介导的免疫功能障碍有助于肿瘤进展并与患者结局相关。转移到肿瘤引流淋巴结（TDLN）是乳腺癌进展的重要步骤，并用于预测患者的预后和生存。虽然淋巴结是重要的免疫器官，但免疫细胞在TDLN中的作用尚未得到彻底研究。我们假设，与淋巴结阳性（NP）患者相比，淋巴结阴性（NN）患者的宿主免疫应答更完整，从而可以抵抗肿瘤侵袭。因此，淋巴结转移除了癌细胞从肿瘤逃逸之外还需要宿主免疫应答的破坏。为了研究NN和NP乳腺癌患者之间的免疫学差异，我们从癌症和免疫细胞相互作用的三个主要区室（肿瘤、TDLN和外周血）中纯化并分析了免疫细胞。与NN患者相比，NP患者的TDLN中与免疫相关通路相关的基因显著下调，与肿瘤促进通路相关的基因显著上调。重要的是，即使在NP患者的无肿瘤TDLN中也可以看到这些特征，这表明这种免疫变化不仅仅是由局部肿瘤侵袭驱动的。此外，在NP患者的肿瘤和血液免疫细胞中也观察到类似的模式，表明NN和NP患者之间的免疫差异是系统性的。总之，这些发现表明，在乳腺癌患者中，整体免疫功能的改变可能是LN转移风险的基础。
Cancer-mediated immune dysfunction contributes to tumor progression and correlates with patient outcome. Metastasis to tumor draining lymph nodes (TDLNs) is an important step in breast cancer progression and is used to predict patient outcome and survival. While lymph nodes are important immune organs, the role of immune cells in TDLNs has not been thoroughly investigated. We hypothesized that the host immune response in node negative (NN) patients is more intact and thereby can resist tumor invasion compared to node positive (NP) patients. As such, lymph node metastasis requires breakdown of the host immune response in addition to escape of cancer cells from the tumor. To investigate the immunological differences between NN and NP breast cancer patients, we purified and profiled immune cells from the three major compartments where cancer and immune cells interact: tumor, TDLNs, and peripheral blood. Significant down-regulation of genes associated with immune-related pathways and up-regulation of genes associated with tumor-promoting pathways was consistently observed in NP patients’ TDLNs compared to NN patients. Importantly, these signatures were seen even in NP patients’ tumor-free TDLNs, suggesting that such immune changes are not driven solely by local tumor invasion. Furthermore, similar patterns were also observed in NP patients’ tumor and blood immune cells, suggesting that immunological differences between NN and NP patients are systemic. Together, these findings suggest that alterations in overall immune function may underlie risk for LN metastasis in breast cancer patients.
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腋窝淋巴结中免疫细胞的特征可以预测乳腺癌中无疾病的生存。
影响因子：
15.8
作者：
Kohrt, HE;Nouri, N;Nowels, K;Johnson, D;Holmes, S;Lee, PP
通讯作者：
Lee, PP
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2.8
作者：
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Saad, Fred
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8.4
作者：
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通讯作者：
Hölzel, D
影响因子：
5.3
作者：
Moutsatsou P;Papavassiliou AG
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Papavassiliou AG
影响因子：
45.3
作者：
Mahmoud, Sahar M. A.;Paish, Emma Claire;Green, Andrew R.
通讯作者：
Green, Andrew R.