A germinal center-associated microenvironmental signature reflects malignant phenotype and outcome of DLBCL.
A germinal center-associated microenvironmental signature reflects malignant phenotype and outcome of DLBCL.
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DOI：
10.1182/bloodadvances.2021004618
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发表时间：
2022-04-12
期刊：
影响因子：
7.5
通讯作者：
Akashi, Koichi
中科院分区：
文献类型：
--
作者：
Miyawaki, Kohta;Kato, Koji;Sugio, Takeshi;Sasaki, Kensuke;Miyoshi, Hiroaki;Semba, Yuichiro;Kikushige, Yoshikane;Mori, Yasuo;Kunisaki, Yuya;Iwasaki, Hiromi;Miyamoto, Toshihiro;Kuo, Frank C.;Aster, Jon C.;Ohshima, Koichi;Maeda, Takahiro;Akashi, Koichi
使用基于nCounter的GC相关微环境基因谱建立DLBCL微环境特征评分系统。DMS评分对DLBCL患者进行分层，具有独立于现有预后模型的不同预后。弥漫性大B细胞淋巴瘤（DLBCL）是最常见的B细胞恶性肿瘤，在金标准利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）之后具有不同的预后。已经建立了几个预后模型，主要集中在淋巴瘤细胞本身的特征，包括细胞的起源（COO），基因组改变，基因/蛋白质表达。然而，淋巴瘤微环境的预后影响及其与淋巴瘤细胞特征的相关性尚未完全了解。使用未经治疗的DLBCL组织的基于nCounter的基因表达谱，我们评估了淋巴瘤微环境对DLBCL临床结局和病理生理学分子特征的临床影响。淋巴瘤组织中正常生发中心（GC）微环境细胞（包括滤泡T细胞、巨噬细胞/树突状细胞和基质细胞）的存在表明治疗反应阳性。我们的预后模型，基于定量的转录物从不同的GC微环境细胞标志物，清楚地确定患者的分级预后独立于现有的预后模型。我们观察到，相对于含有GC微环境细胞的DLBCL组织，缺乏GC微环境细胞的DLBCL组织中与预后不良相关的基因组改变和异常基因表达的发生率增加。这些数据表明，GC相关微环境特征的丧失决定了DLBCL患者的临床结果，反映了“不利”分子特征的积累。
The DLBCL microenvironment signature scoring system was established using nCounter-based profiling of GC-related microenvironmental genes. DMS scores stratified DLBCL patients with different prognosis independently of existing prognostic models. Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy, with varying prognosis after the gold standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Several prognostic models have been established by focusing primarily on characteristics of lymphoma cells themselves, including cell-of-origin (COO), genomic alterations, and gene/protein expressions. However, the prognostic impact of the lymphoma microenvironment and its association with characteristics of lymphoma cells are not fully understood. Using the nCounter-based gene expression profiling of untreated DLBCL tissues, we assess the clinical impact of lymphoma microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL. The presence of normal germinal center (GC)-microenvironmental cells, including follicular T cells, macrophage/dendritic cells, and stromal cells in lymphoma tissue indicates a positive therapeutic response. Our prognostic model, based on quantitation of transcripts from distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis independently of existing prognostic models. We observed increased incidences of genomic alterations and aberrant gene expression associated with poor prognosis in DLBCL tissues lacking GC-microenvironmental cells relative to those containing these cells. These data suggest that the loss of GC-associated microenvironmental signature dictates clinical outcomes of DLBCL patients reflecting the accumulation of “unfavorable” molecular signatures.
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影响因子：
1.2
作者：
Araie, Hiroaki;Sakamaki, Ippei;Yamauchi, Takahiro
通讯作者：
Yamauchi, Takahiro
DOI：
10.1038/nri3804
发表时间：
2015-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1093/annonc/mdy450
发表时间：
2018-12-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Ciavarella S;Vegliante MC;Fabbri M;De Summa S;Melle F;Motta G;De Iuliis V;Opinto G;Enjuanes A;Rega S;Gulino A;Agostinelli C;Scattone A;Tommasi S;Mangia A;Mele F;Simone G;Zito AF;Ingravallo G;Vitolo U;Chiappella A;Tarella C;Gianni AM;Rambaldi A;Zinzani PL;Casadei B;Derenzini E;Loseto G;Pileri A;Tabanelli V;Fiori S;Rivas-Delgado A;López-Guillermo A;Venesio T;Sapino A;Campo E;Tripodo C;Guarini A;Pileri SA
通讯作者：
Pileri SA
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
32.4
作者：
Baratin, Myriam;Simon, Lea;Bajenoff, Marc
通讯作者：
Bajenoff, Marc