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 1 , Benjamin Rengstl 1 , Claudia Doring 1 , Julia Bein 1 , Sebastian Newrzela 1 , Uta Brunnberg 2 , Hans Michael Kvasnicka 1 , Martine Vornanen 3 , Ralf Kuppers 4 , Martin-Leo Hansmann 1 , Sylvia Hartmann 1 1 Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany 2 Department of Internal Medicine 2, Hospital of the J. W. Goethe University, Frankfurt am Main, Germany 3 Department of Pathology, Tampere University Hospital and University of Tampere, Tampere, Finland 4 Institute 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.