title: Epstein-Barr virus infection induces an increase of T regulatory type 1 cells in Hodgkin lymphoma patients.
abstract: Epstein-Barr Virus (EBV) is present in the neoplastic cells of around 20-30% of patients with Hodgkin Lymphoma (HL). Although, an immunosuppressive environment is currently described in HL patients, little is known concerning the regulatory mechanism induced by EBV proteins expression in tumour cells. This study aimed to investigate an association between regulatory Type 1 cells (Tr1) and EBV tissue positivity in HL patients. Transcriptomic analysis of both EBV-positive and EBV-negative tumours showed that EBV infection increased gene expression of Tr1-related markers (ITGA2, ITGB2, LAG3) and associated-immunosuppressive cytokines (IL10). This up-regulation was associated with an over-expression of several chemokine markers known to attract T-helper type 2 (Th2) and regulatory T cells thus contributing to immune suppression. This Tr1 cells recruitment in EBV-positive HL was confirmed by immunohistochemical analysis of frozen nodes biopsies and by flow cytometric analysis of peripheral blood mononuclear cells of EBV-positive patients. Additionally, we showed that IL10 production was significantly enhanced in tumours and blood of EBV-positive HL patients. Our results propose a new model in which EBV can recruit Tr1 cells to the nodes' microenvironment, suggesting that the expression of EBV proteins in tumour cells could enable the escape of EBV-infected tumour cells from the virus-specific CTL response.
authors.affiliation: Institut de Biologie de Lille, UMR 8161, CNRS, Institut Pasteur de Lille, Université Lille-Nord de France, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Morales
authors.forename: Dhafer
authors.initials: D
authors.lastname: Mrizak
authors.forename: Violaine
authors.initials: V
authors.lastname: François
authors.forename: Rami
authors.initials: R
authors.lastname: Mustapha
authors.forename: Céline
authors.initials: C
authors.lastname: Miroux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Depil
authors.forename: Anne-Valérie
authors.initials: AV
authors.lastname: Decouvelaere
authors.forename: Pauline
authors.initials: P
authors.lastname: Lionne-Huyghe
authors.forename: Claude
authors.initials: C
authors.lastname: Auriault
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.forename: Véronique
authors.initials: V
authors.lastname: Pancré
authors.forename: Nadira
authors.initials: N
authors.lastname: Delhem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000821:virology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines
keywords: Epstein-Barr Virus; Hodgkin lymphoma; IL10; Tr1; chemokines