Oncotarget

Research Papers:

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

Bianca Schuhmacher, Benjamin Rengstl, Claudia Döring, Julia Bein, Sebastian Newrzela, Uta Brunnberg, Hans Michael Kvasnicka, Martine Vornanen, Ralf Küppers, Martin-Leo Hansmann and Sylvia Hartmann _

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Oncotarget. 2016; 7:72197-72210. https://doi.org/10.18632/oncotarget.12363

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Abstract

Bianca Schuhmacher1, Benjamin Rengstl1, Claudia Döring1, Julia Bein1, Sebastian Newrzela1, Uta Brunnberg2, Hans Michael Kvasnicka1, Martine Vornanen3, Ralf Küppers4, Martin-Leo Hansmann1, Sylvia Hartmann1

1Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany

2Department of Internal Medicine 2, Hospital of the J. W. Goethe University, Frankfurt am Main, Germany

3Department of Pathology, Tampere University Hospital and University of Tampere, Tampere, Finland

4Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany

Correspondence to:

Sylvia Hartmann, email: s.hartmann@em.uni-frankfurt.de

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

Received: July 22, 2016    Accepted: September 19, 2016    Published: September 30, 2016

ABSTRACT

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.


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