A strong host response and lack of MYC expression are characteristic for diffuse large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin lymphoma
A strong host response and lack of MYC expression are characteristic for diffuse large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin lymphoma
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DOI：
10.18632/oncotarget.12363
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Hartmann, Sylvia
中科院分区：
文献类型：
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作者：
Schuhmacher, Bianca;Rengstl, Benjamin;Hartmann, Sylvia
结节淋巴细胞占优势的霍奇金淋巴瘤(NLPHL)是一种惰性淋巴瘤，但可转化为弥漫性大B细胞淋巴瘤(DLBCL)，表现出更具侵袭性的临床行为。在分子水平上，人们对这些病例知之甚少。因此，本研究的目的是通过基因表达谱(GEP)对NLPHL转化的DLBCL(LP-DLBCL)进行鉴定。GEP显示了一个针对特定宿主反应的炎性签名。在与宿主反应相似的共培养模型中，DEV肿瘤细胞的生长行为受到损害。肿瘤细胞增殖减少的机制包括下调MYC及其靶基因。免疫组织化学显示12/16例LP-DLBCL中MYC表达缺失。CD274/PD-L1与T细胞或单核细胞共培养后在DEV肿瘤细胞中表达上调，在19例LP-DLBCL中有12例表达阳性。因此，我们的数据为LP-DLBCL的发病机制提供了新的见解，并解释了相对较低的肿瘤细胞含量。此外，研究结果表明，用免疫检查点抑制剂治疗这些患者可能会增强这些患者已经在进行的宿主反应。
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP revealed an inflammatory signature pinpointing to a specific host response. In a coculture model resembling this host response, DEV tumor cells showed an impaired growth behavior. Mechanisms involved in the reduced tumor cell proliferation included a downregulation of MYC and its target genes. Lack of MYC expression was also confirmed in 12/16 LP-DLBCL by immunohistochemistry. Furthermore, CD274/PD-L1 was upregulated in DEV tumor cells after coculture with T cells or monocytes and its expression was validated in 12/19 cases of LP-DLBCL. Thereby, our data provide new insights into the pathogenesis of LP-DLBCL and an explanation for the relatively low tumor cell content. Moreover, the findings suggest that treatment of these patients with immune checkpoint inhibitors may enhance an already ongoing host response in these patients.