Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome
Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome
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DOI：
10.1182/blood-2008-07-168096
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发表时间：
2009-03-19
期刊：
影响因子：
20.3
通讯作者：
Xerri, Luc
中科院分区：
文献类型：
--
作者：
Chetaille, Bruno;Bertucci, Francois;Xerri, Luc
经典霍奇金淋巴瘤（cHL）患者的结局可能与肿瘤微环境有关，而肿瘤微环境又可能受到EB病毒（EBV）感染的影响。为了表征cHL微环境，使用DNA微阵列分析了一组63个cHL组织样本。它们的基因表达谱不同于用作对照的富含组织细胞T细胞的B细胞淋巴瘤（H/TCRBCL）样品，主要是由于H/TCRBCL中PDCD 1/PD-1的高表达。EBV+ cHL组织可以通过Th 1和抗病毒应答的基因特征与EBV-样品区分开。来自具有良好结局的cHL患者的样本过表达B细胞特异性基因和凋亡途径相关基因。使用免疫组织化学分析了一组独立的146份cHL样本。在TIA-1（+）-反应性细胞或拓扑异构酶-2（+）肿瘤细胞的高百分比的情况下，其显示出显著的不利值，而BCL 11 A（+）、FOXP 3（+）或CD 20（+）反应性细胞的高数目具有有利的影响。我们的研究结果表明，B细胞在cHL微环境中的抗肿瘤作用和H/TCRBCL中PD 1通路比cHL更强的基质影响。EBV+ cHL组织中Th 1/抗病毒应答的观察为新的治疗策略提供了基础。（血。2009;113：2765-2775）
The outcome of classical Hodgkin lymphoma (cHL) patients may be related to the tumor microenvironment, which in turn may be influenced by Epstein-Barr virus (EBV) infection. To characterize the cHL microenvironment, a set of 63 cHL tissue samples was profiled using DNA microarrays. Their gene expression profile differed from that of histiocyte T cell rich B-cell lymphoma (H/TCRBCL) samples that were used as controls, mainly due to high expression of PDCD1/PD-1 in H/TCRBCL. EBV+ cHL tissues could be distinguished from EBV- samples by a gene signature characteristic of Th1 and antiviral responses. Samples from cHL patients with favorable outcome overexpressed genes specific for B cells and genes involved in apoptotic pathways. An independent set of 146 cHL samples was analyzed using immunohistochemistry. It showed a significant adverse value in case of high percentage of either TIA-1(+)-reactive cells or topoisomerase-2(+) tumor cells, whereas high numbers of BCL11A(+), FOXP3(+), or CD20(+) reactive cells had a favorable influence. Our results suggest an antitumoral role for B cells in the cHL microenvironment and a stronger stromal influence of the PD1 pathway in H/TCRBCL than cHL. The observation of Th1/antiviral response in EBV+ cHL tissues provides a basis for novel treatment strategies. (Blood. 2009;113:2765-2775)