GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features
GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features
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DOI：
10.1182/blood-2013-12-544809
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发表时间：
2014-05-08
期刊：
影响因子：
20.3
通讯作者：
Wilcox, Ryan A.
中科院分区：
文献类型：
--
作者：
Wang, Tianjiao;Feldman, Andrew L.;Wilcox, Ryan A.
对于最常见的外周T细胞淋巴瘤（PTCL），起源细胞和肿瘤微环境的作用仍然难以捉摸。由于巨噬细胞促进恶性T细胞的生长和存活，并且是肿瘤微环境的丰富成分，因此在T细胞淋巴增殖性疾病中检查了它们的功能极化。观察到肿瘤微环境中丰富的细胞因子，特别是白细胞介素（IL）-10，可促进巨噬细胞的交替极化。巨噬细胞极化是信号转导子和转录激活子3依赖性的，并且受到Janus激酶抑制剂ruxolitinib的损害。在常规T细胞中，T辅助细胞（Th）2相关细胞因子和IL-10的产生（两者均促进巨噬细胞交替极化）受T细胞转录因子GATA结合蛋白3（加塔-3）调节。因此，研究了其在T细胞淋巴瘤中的作用。在45%的PTCL中观察到加塔-3表达，未另行说明（PTCL，NOS），并与不同的分子特征相关，包括Th 2相关细胞因子的产生。此外，加塔-3表达鉴定了具有不同临床特征的PTCL，NOS亚组，包括较差的无进展生存期和总生存期。总的来说，这些数据表明，进一步了解T细胞淋巴瘤中的细胞起源和淋巴细胞个体发生可能会提高我们对这些侵袭性淋巴瘤中肿瘤微环境致病作用的理解。
The cell of origin and the tumor microenvironment's role remain elusive for the most common peripheral T-cell lymphomas (PTCLs). As macrophages promote the growth and survival of malignant T cells and are abundant constituents of the tumor microenvironment, their functional polarization was examined in T-cell lymphoproliferative disorders. Cytokines that are abundant within the tumor microenvironment, particularly interleukin (IL)-10, were observed to promote alternative macrophage polarization. Macrophage polarization was signal transducer and activator of transcription 3 dependent and was impaired by the Janus kinase inhibitor ruxolitinib. In conventional T cells, the production of T helper (Th)2-associated cytokines and IL-10, both of which promote alternative macrophage polarization, is regulated by the T-cell transcription factor GATA-binding protein 3 (GATA-3). Therefore, its role in the T-cell lymphomas was examined. GATA-3 expression was observed in 45% of PTCLs, not otherwise specified (PTCL, NOS) and was associated with distinct molecular features, including the production of Th2-associated cytokines. In addition, GATA-3 expression identified a subset of PTCL, NOS with distinct clinical features, including inferior progression-free and overall survival. Collectively, these data suggest that further understanding the cell of origin and lymphocyte ontogeny among the T-cell lymphomas may improve our understanding of the tumor microenvironment's pathogenic role in these aggressive lymphomas.