Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact

Autores
Cohen, Melina; Vistarop, Aldana Georgina; Huaman, Fuad; Narbaitz, Marina; Metrebian, Fernanda; de Matteo, Elena Noemí; Preciado, María Victoria; Chabay, Paola Andrea
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.
Fil: Cohen, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Vistarop, Aldana Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Huaman, Fuad. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Narbaitz, Marina. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Metrebian, Fernanda. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: de Matteo, Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Preciado, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Chabay, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Materia
B Cell Lymphoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/73431
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impactCohen, MelinaVistarop, Aldana GeorginaHuaman, FuadNarbaitz, MarinaMetrebian, Fernandade Matteo, Elena NoemíPreciado, María VictoriaChabay, Paola AndreaB Cell Lymphomahttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.Fil: Cohen, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; ArgentinaFil: Vistarop, Aldana Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; ArgentinaFil: Huaman, Fuad. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Narbaitz, Marina. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Metrebian, Fernanda. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: de Matteo, Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; ArgentinaFil: Preciado, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; ArgentinaFil: Chabay, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; ArgentinaNature Publishing Group2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/73431Cohen, Melina; Vistarop, Aldana Georgina; Huaman, Fuad; Narbaitz, Marina; Metrebian, Fernanda; et al.; Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact; Nature Publishing Group; Scientific Reports; 7; 10813; 12-2017; 1-102045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-017-11052-zinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-11052-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:15Zoai:ri.conicet.gov.ar:11336/73431instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:56:15.35CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
title Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
spellingShingle Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
Cohen, Melina
B Cell Lymphoma
title_short Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
title_full Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
title_fullStr Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
title_full_unstemmed Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
title_sort Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact
dc.creator.none.fl_str_mv Cohen, Melina
Vistarop, Aldana Georgina
Huaman, Fuad
Narbaitz, Marina
Metrebian, Fernanda
de Matteo, Elena Noemí
Preciado, María Victoria
Chabay, Paola Andrea
author Cohen, Melina
author_facet Cohen, Melina
Vistarop, Aldana Georgina
Huaman, Fuad
Narbaitz, Marina
Metrebian, Fernanda
de Matteo, Elena Noemí
Preciado, María Victoria
Chabay, Paola Andrea
author_role author
author2 Vistarop, Aldana Georgina
Huaman, Fuad
Narbaitz, Marina
Metrebian, Fernanda
de Matteo, Elena Noemí
Preciado, María Victoria
Chabay, Paola Andrea
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv B Cell Lymphoma
topic B Cell Lymphoma
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.
Fil: Cohen, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Vistarop, Aldana Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Huaman, Fuad. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Narbaitz, Marina. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Metrebian, Fernanda. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: de Matteo, Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Preciado, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
Fil: Chabay, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina
description Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/73431
Cohen, Melina; Vistarop, Aldana Georgina; Huaman, Fuad; Narbaitz, Marina; Metrebian, Fernanda; et al.; Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact; Nature Publishing Group; Scientific Reports; 7; 10813; 12-2017; 1-10
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/73431
identifier_str_mv Cohen, Melina; Vistarop, Aldana Georgina; Huaman, Fuad; Narbaitz, Marina; Metrebian, Fernanda; et al.; Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: Clinical features and survival impact; Nature Publishing Group; Scientific Reports; 7; 10813; 12-2017; 1-10
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-017-11052-z
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-11052-z
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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