A strong host response and lack of MYC expression are characteristic for diffuse large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin lymphoma

作者：Schuhmacher Bianca; Rengstl Benjamin; Doering Claudia; Bein Julia; Newrzela Sebastian; Brunnberg Uta; Kvasnicka Hans Michael; Vornanen Martine; Kueppers Ralf; Hansmann Martin Leo; Hartmann Sylvia^*

来源：Oncotarget, 2016, 7(44): 72197-72210.

DOI：10.18632/oncotarget.12363

• nodular lymphocyte predominant Hodgkin lymphoma
• diffuse large B cell lymphoma
• T cell/histiocyte rich large B cell lymphoma
• host response
• gene expression profiling

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.

• 出版日期2016-11-1