Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function

Autores
Gatti, Gerardo Alberto; Núñez, Nicolás; Nocera, David Andres; Dejader, Lien; Libert, Claude; Giraudo, Constancio Alberto; Maccioni, Mariana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine–polycytidylic acid (poly I:C) and polyadenylic–polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine loop, dsRNA-elicited IFN-β production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN-β at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN-β produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN-γ production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3−/− mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1−/− mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN-β production and contribute to the antitumoral response.
Fil: Gatti, Gerardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Núñez, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nocera, David Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Dejader, Lien. University of Ghent; Bélgica
Fil: Libert, Claude. University of Ghent; Bélgica
Fil: Giraudo, Constancio Alberto. Fundación Para El Progreso de la Medicina; Argentina
Fil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
Ifnbeta
Dsrna
Tlr3
Dendritic Cells
Tumor Immunity
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:11336/25788
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/25788
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell functionGatti, Gerardo AlbertoNúñez, NicolásNocera, David AndresDejader, LienLibert, ClaudeGiraudo, Constancio AlbertoMaccioni, MarianaIfnbetaDsrnaTlr3Dendritic CellsTumor Immunityhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine–polycytidylic acid (poly I:C) and polyadenylic–polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine loop, dsRNA-elicited IFN-β production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN-β at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN-β produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN-γ production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3−/− mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1−/− mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN-β production and contribute to the antitumoral response.Fil: Gatti, Gerardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Núñez, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nocera, David Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Dejader, Lien. University of Ghent; BélgicaFil: Libert, Claude. University of Ghent; BélgicaFil: Giraudo, Constancio Alberto. Fundación Para El Progreso de la Medicina; ArgentinaFil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaWiley VCH Verlag2013-05info: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/11336/25788Gatti, Gerardo Alberto; Núñez, Nicolás; Nocera, David Andres; Dejader, Lien; Libert, Claude; et al.; Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function; Wiley VCH Verlag; European Journal of Immunology; 43; 7; 5-2013; 1849-18610014-2980CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/eji.201242902info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201242902/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:24:58Zoai:ri.conicet.gov.ar:11336/25788instacron: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 10:24:59.221CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
title Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
spellingShingle Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
Gatti, Gerardo Alberto
Ifnbeta
Dsrna
Tlr3
Dendritic Cells
Tumor Immunity
title_short Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
title_full Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
title_fullStr Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
title_full_unstemmed Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
title_sort Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function
dc.creator.none.fl_str_mv Gatti, Gerardo Alberto
Núñez, Nicolás
Nocera, David Andres
Dejader, Lien
Libert, Claude
Giraudo, Constancio Alberto
Maccioni, Mariana
author Gatti, Gerardo Alberto
author_facet Gatti, Gerardo Alberto
Núñez, Nicolás
Nocera, David Andres
Dejader, Lien
Libert, Claude
Giraudo, Constancio Alberto
Maccioni, Mariana
author_role author
author2 Núñez, Nicolás
Nocera, David Andres
Dejader, Lien
Libert, Claude
Giraudo, Constancio Alberto
Maccioni, Mariana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Ifnbeta
Dsrna
Tlr3
Dendritic Cells
Tumor Immunity
topic Ifnbeta
Dsrna
Tlr3
Dendritic Cells
Tumor Immunity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine–polycytidylic acid (poly I:C) and polyadenylic–polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine loop, dsRNA-elicited IFN-β production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN-β at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN-β produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN-γ production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3−/− mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1−/− mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN-β production and contribute to the antitumoral response.
Fil: Gatti, Gerardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Núñez, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nocera, David Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Dejader, Lien. University of Ghent; Bélgica
Fil: Libert, Claude. University of Ghent; Bélgica
Fil: Giraudo, Constancio Alberto. Fundación Para El Progreso de la Medicina; Argentina
Fil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine–polycytidylic acid (poly I:C) and polyadenylic–polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine loop, dsRNA-elicited IFN-β production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN-β at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN-β produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN-γ production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3−/− mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1−/− mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN-β production and contribute to the antitumoral response.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
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/11336/25788
Gatti, Gerardo Alberto; Núñez, Nicolás; Nocera, David Andres; Dejader, Lien; Libert, Claude; et al.; Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function; Wiley VCH Verlag; European Journal of Immunology; 43; 7; 5-2013; 1849-1861
0014-2980
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25788
identifier_str_mv Gatti, Gerardo Alberto; Núñez, Nicolás; Nocera, David Andres; Dejader, Lien; Libert, Claude; et al.; Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function; Wiley VCH Verlag; European Journal of Immunology; 43; 7; 5-2013; 1849-1861
0014-2980
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/eji.201242902
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201242902/abstract
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
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
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 13.070432

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