The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma

Autores
Juszczynski, Przemyslaw; Ouyang, Jing; Monti, Stefano; Rodig, Scott J.; Takeyama, Kunihiko; Abramson, Jeremy; Chen, Wen; Kutok, Jeffery; Rabinovich, Gabriel Adrián; Shipp, Margaret
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Classical Hodgkin lymphomas (cHLs) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate that includes abundant T helper (Th)-2 and T regulatory (Treg) cells. The skewed nature of the T cell infiltrate and the lack of an effective host antitumor immune response suggest that RS cells use potent mechanisms to evade immune attack. In a screen for T cell-inhibitory molecules in cHL, we found that RS cells selectively overexpressed the immunoregulatory glycan-binding protein, galectin-1 (Gal1), through an AP1-dependent enhancer. In cocultures of activated T cells and Hodgkin cell lines, RNAi-mediated blockade of RS cell Gal1 increased T cell viability and restored the Th1/Th2 balance. In contrast, Gal1 treatment of activated T cells favored the secretion of Th2 cytokines and the expansion of CD4+CD25high FOXP3+ Treg cells. These data directly implicate RS cell Gal1 in the development and maintenance of an immunosuppressive Th2/Treg-skewed microenvironment in cHL and provide the molecular basis for selective Gal1 expression in RS cells. Thus, Gal1 represents a potential therapeutic target for restoring immune surveillance in cHL.
Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados Unidos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: Monti, Stefano. Brigham and Women; Estados Unidos
Fil: Rodig, Scott J.. Brigham and Women; Estados Unidos
Fil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados Unidos
Fil: Abramson, Jeremy. Dana Farber Cancer Institute; Estados Unidos
Fil: Chen, Wen. Dana Farber Cancer Institute; Estados Unidos
Fil: Kutok, Jeffery. Broad Institute; Estados Unidos
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Shipp, Margaret. Dana Farber Cancer Institute; Estados Unidos
Materia
GALECTIN-1
HODKING DISEASE
IMMUNE TOLERANCE
CYTOKINES
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:11336/27507
Acceder
id CONICETDig_664b442a433cbc9301f24f597b692238
oai_identifier_str oai:ri.conicet.gov.ar:11336/27507
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphomaJuszczynski, PrzemyslawOuyang, JingMonti, StefanoRodig, Scott J.Takeyama, KunihikoAbramson, JeremyChen, WenKutok, JefferyRabinovich, Gabriel AdriánShipp, MargaretGALECTIN-1HODKING DISEASEIMMUNE TOLERANCECYTOKINEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Classical Hodgkin lymphomas (cHLs) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate that includes abundant T helper (Th)-2 and T regulatory (Treg) cells. The skewed nature of the T cell infiltrate and the lack of an effective host antitumor immune response suggest that RS cells use potent mechanisms to evade immune attack. In a screen for T cell-inhibitory molecules in cHL, we found that RS cells selectively overexpressed the immunoregulatory glycan-binding protein, galectin-1 (Gal1), through an AP1-dependent enhancer. In cocultures of activated T cells and Hodgkin cell lines, RNAi-mediated blockade of RS cell Gal1 increased T cell viability and restored the Th1/Th2 balance. In contrast, Gal1 treatment of activated T cells favored the secretion of Th2 cytokines and the expansion of CD4+CD25high FOXP3+ Treg cells. These data directly implicate RS cell Gal1 in the development and maintenance of an immunosuppressive Th2/Treg-skewed microenvironment in cHL and provide the molecular basis for selective Gal1 expression in RS cells. Thus, Gal1 represents a potential therapeutic target for restoring immune surveillance in cHL.Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados UnidosFil: Ouyang, Jing. Dana Farber Cancer Institute; Estados UnidosFil: Monti, Stefano. Brigham and Women; Estados UnidosFil: Rodig, Scott J.. Brigham and Women; Estados UnidosFil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados UnidosFil: Abramson, Jeremy. Dana Farber Cancer Institute; Estados UnidosFil: Chen, Wen. Dana Farber Cancer Institute; Estados UnidosFil: Kutok, Jeffery. Broad Institute; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Shipp, Margaret. Dana Farber Cancer Institute; Estados UnidosNational Academy of Sciences2007-08-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/27507Juszczynski, Przemyslaw; Ouyang, Jing; Monti, Stefano; Rodig, Scott J.; Takeyama, Kunihiko; et al.; The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 104; 32; 7-8-2007; 13134-131390027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/104/32/13134.shortinfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0706017104info:eu-repo/semantics/altIdentifier/pmid/10.1073/pnas.0706017104info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:10:09Zoai:ri.conicet.gov.ar:11336/27507instacron: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:34982025-10-15 15:10:09.8CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
title The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
spellingShingle The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
Juszczynski, Przemyslaw
GALECTIN-1
HODKING DISEASE
IMMUNE TOLERANCE
CYTOKINES
title_short The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
title_full The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
title_fullStr The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
title_full_unstemmed The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
title_sort The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
dc.creator.none.fl_str_mv Juszczynski, Przemyslaw
Ouyang, Jing
Monti, Stefano
Rodig, Scott J.
Takeyama, Kunihiko
Abramson, Jeremy
Chen, Wen
Kutok, Jeffery
Rabinovich, Gabriel Adrián
Shipp, Margaret
author Juszczynski, Przemyslaw
author_facet Juszczynski, Przemyslaw
Ouyang, Jing
Monti, Stefano
Rodig, Scott J.
Takeyama, Kunihiko
Abramson, Jeremy
Chen, Wen
Kutok, Jeffery
Rabinovich, Gabriel Adrián
Shipp, Margaret
author_role author
author2 Ouyang, Jing
Monti, Stefano
Rodig, Scott J.
Takeyama, Kunihiko
Abramson, Jeremy
Chen, Wen
Kutok, Jeffery
Rabinovich, Gabriel Adrián
Shipp, Margaret
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GALECTIN-1
HODKING DISEASE
IMMUNE TOLERANCE
CYTOKINES
topic GALECTIN-1
HODKING DISEASE
IMMUNE TOLERANCE
CYTOKINES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Classical Hodgkin lymphomas (cHLs) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate that includes abundant T helper (Th)-2 and T regulatory (Treg) cells. The skewed nature of the T cell infiltrate and the lack of an effective host antitumor immune response suggest that RS cells use potent mechanisms to evade immune attack. In a screen for T cell-inhibitory molecules in cHL, we found that RS cells selectively overexpressed the immunoregulatory glycan-binding protein, galectin-1 (Gal1), through an AP1-dependent enhancer. In cocultures of activated T cells and Hodgkin cell lines, RNAi-mediated blockade of RS cell Gal1 increased T cell viability and restored the Th1/Th2 balance. In contrast, Gal1 treatment of activated T cells favored the secretion of Th2 cytokines and the expansion of CD4+CD25high FOXP3+ Treg cells. These data directly implicate RS cell Gal1 in the development and maintenance of an immunosuppressive Th2/Treg-skewed microenvironment in cHL and provide the molecular basis for selective Gal1 expression in RS cells. Thus, Gal1 represents a potential therapeutic target for restoring immune surveillance in cHL.
Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados Unidos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: Monti, Stefano. Brigham and Women; Estados Unidos
Fil: Rodig, Scott J.. Brigham and Women; Estados Unidos
Fil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados Unidos
Fil: Abramson, Jeremy. Dana Farber Cancer Institute; Estados Unidos
Fil: Chen, Wen. Dana Farber Cancer Institute; Estados Unidos
Fil: Kutok, Jeffery. Broad Institute; Estados Unidos
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Shipp, Margaret. Dana Farber Cancer Institute; Estados Unidos
description Classical Hodgkin lymphomas (cHLs) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate that includes abundant T helper (Th)-2 and T regulatory (Treg) cells. The skewed nature of the T cell infiltrate and the lack of an effective host antitumor immune response suggest that RS cells use potent mechanisms to evade immune attack. In a screen for T cell-inhibitory molecules in cHL, we found that RS cells selectively overexpressed the immunoregulatory glycan-binding protein, galectin-1 (Gal1), through an AP1-dependent enhancer. In cocultures of activated T cells and Hodgkin cell lines, RNAi-mediated blockade of RS cell Gal1 increased T cell viability and restored the Th1/Th2 balance. In contrast, Gal1 treatment of activated T cells favored the secretion of Th2 cytokines and the expansion of CD4+CD25high FOXP3+ Treg cells. These data directly implicate RS cell Gal1 in the development and maintenance of an immunosuppressive Th2/Treg-skewed microenvironment in cHL and provide the molecular basis for selective Gal1 expression in RS cells. Thus, Gal1 represents a potential therapeutic target for restoring immune surveillance in cHL.
publishDate 2007
dc.date.none.fl_str_mv 2007-08-07
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/11336/27507
Juszczynski, Przemyslaw; Ouyang, Jing; Monti, Stefano; Rodig, Scott J.; Takeyama, Kunihiko; et al.; The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 104; 32; 7-8-2007; 13134-13139
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/27507
identifier_str_mv Juszczynski, Przemyslaw; Ouyang, Jing; Monti, Stefano; Rodig, Scott J.; Takeyama, Kunihiko; et al.; The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 104; 32; 7-8-2007; 13134-13139
0027-8424
1091-6490
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.pnas.org/content/104/32/13134.short
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0706017104
info:eu-repo/semantics/altIdentifier/pmid/10.1073/pnas.0706017104
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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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score 13.22299

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