title: Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome.
abstract: The outcome of classical Hodgkin lymphoma (cHL) patients may be related to the tumor microenvironment, which in turn may be influenced by Epstein-Barr virus (EBV) infection. To characterize the cHL microenvironment, a set of 63 cHL tissue samples was profiled using DNA microarrays. Their gene expression profile differed from that of histiocyte T cell-rich B-cell lymphoma (H/TCRBCL) samples that were used as controls, mainly due to high expression of PDCD1/PD-1 in H/TCRBCL. EBV(+) cHL tissues could be distinguished from EBV(-) samples by a gene signature characteristic of Th1 and antiviral responses. Samples from cHL patients with favorable outcome overexpressed genes specific for B cells and genes involved in apoptotic pathways. An independent set of 146 cHL samples was analyzed using immunohistochemistry. It showed a significant adverse value in case of high percentage of either TIA-1(+)-reactive cells or topoisomerase-2(+) tumor cells, whereas high numbers of BCL11A(+), FOXP3(+), or CD20(+) reactive cells had a favorable influence. Our results suggest an antitumoral role for B cells in the cHL microenvironment and a stronger stromal influence of the PD1 pathway in H/TCRBCL than cHL. The observation of Th1/ antiviral response in EBV(+) cHL tissues provides a basis for novel treatment strategies.
authors.affiliation: Department of Bio-Pathology, Institut Paoli-Calmettes and Université de la Méditerranée, Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Chetaille
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Picquenot
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Frank
authors.initials: F
authors.lastname: Morschhauser
authors.forename: Olivier
authors.initials: O
authors.lastname: Casasnovas
authors.forename: Tony
authors.initials: T
authors.lastname: Petrella
authors.forename: Thierry
authors.initials: T
authors.lastname: Molina
authors.forename: Anne
authors.initials: A
authors.lastname: Vekhoff
authors.forename: Pierre
authors.initials: P
authors.lastname: Feugier
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000145:classification / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D012074:Remission Induction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins