12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?

12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?
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DOI:
10.1038/srep00765
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发表时间:
2012
期刊:
影响因子:
4.6
通讯作者:
Mule, James J.
Mule, James J.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Messina, Jane L.;Fenstermacher, David A.;Eschrich, Steven;Qu, Xiaotao;Berglund, Anders E.;Lloyd, Mark C.;Schell, Michael J.;Sondak, Vernon K.;Weber, Jeffrey S.;Mule, James J.

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我们在14,492个不同实体瘤的基因组阵列上询问了12种趋化因子基因表达特征(GES),并显示出在不同组织学中的广泛分布。我们假设,这种12-趋化因子GES可能准确地预测一个独特的肿瘤内免疫反应,在第四阶段(非局部)黑色素瘤转移。12-趋化因子GES预测存在独特的淋巴结样结构,包含CD 20 + B细胞滤泡和显著的CD 3 + T细胞区域(CD 4+和CD 8+亚群)。CD 86+,但不是FoxP 3+,细胞也存在于这些独特的结构中。12-趋化因子GES评分与存在独特的淋巴结结构之间的直接相关性也与黑色素瘤患者亚组的较好总体生存率相关。这种新型12-趋化因子GES的使用可能会揭示抗肿瘤免疫反应原位机制的基本信息,可能会改善最适合免疫治疗的黑色素瘤患者的识别和选择。
We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20+ B cell follicles with prominent areas of CD3+ T cells (both CD4+ and CD8+ subsets). CD86+, but not FoxP3+, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.
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