title: A strong host response and lack of MYC expression are characteristic for diffuse large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin lymphoma.
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.
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schuhmacher
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rengstl
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Döring
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bein
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Newrzela
authors.affiliation: Department of Internal Medicine 2, Hospital of the J. W. Goethe University, Frankfurt am Main, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Brunnberg
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Kvasnicka
authors.affiliation: Department of Pathology, Tampere University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Martine
authors.initials: M
authors.lastname: Vornanen
authors.affiliation: Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism; D001706:Biopsy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D018920:Coculture Techniques; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D008198:Lymph Nodes; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc
keywords: T cell/histiocyte rich large B cell lymphoma; diffuse large B cell lymphoma; gene expression profiling; host response; nodular lymphocyte predominant Hodgkin lymphoma