TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity

Autores
Roselli, Emiliano; Araya, Paula; Núñez, Nicolás; Gatti, Gerardo Alberto; Graziano, Francesca; Sedlik, Christine; Benaroch, Philippe; Piaggio, Eliane; Maccioni, Mariana
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
An important challenge in cancer immunotherapy is to expand the number of patients that benefit from immune checkpoint inhibitors (CI), a fact that has been related to the pre-existence of an efficient antitumor immune response. Different strategies are being proposed to promote tumor immunity and to be used in combined therapies with CI. Recently, we reported that intratumoral administration of naked poly A:U, a dsRNA mimetic empirically used in early clinical trials with some success, delays tumor growth and prolongs mice survival in several murine cancer models. Here, we show that CD103+ cDC1 and, to a much lesser extent CD11b+ cDC2, are the only populations expressing TLR3 at the tumor site, and consequently could be potential targets of poly A:U. Upon poly A:U administration these cells become activated and elicit profound changes in the composition of the tumor immune infiltrate, switching the immune suppressive tumor environment to anti-tumor immunity. The sole administration of naked poly A:U promotes striking changes within the lymphoid compartment, with all the anti-tumoral parameters being enhanced: a higher frequency of CD8+ Granzyme B+ T cells, (lower Treg/CD8+ ratio) and an important expansion of tumor-antigen specific CD8+ T cells. Also, PD1/PDL1 showed an increased expression indicating that neutralization of this axis could be exploited in combination with poly A:U. Our results shed new light to promote further assays in this dsRNA mimetic to the clinical field.
Fil: Roselli, Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Araya, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Núñez, Nicolás. Institute Of Experimental Immunology; Suiza. Universitat Zurich; Suiza
Fil: Gatti, Gerardo Alberto. Fundación Para El Progreso de la Medicina; Argentina
Fil: Graziano, Francesca. Instituto Curie; Francia
Fil: Sedlik, Christine. Instituto Curie; Francia
Fil: Benaroch, Philippe. Instituto Curie; Francia
Fil: Piaggio, Eliane. Instituto Curie; Francia
Fil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
CANCER IMMUNOTHERAPY
CD103+ CDC1
DSRNA MIMETICS
TLR3
TUMOR-INFILTRATE
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:11336/129076
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/129076
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunityRoselli, EmilianoAraya, PaulaNúñez, NicolásGatti, Gerardo AlbertoGraziano, FrancescaSedlik, ChristineBenaroch, PhilippePiaggio, ElianeMaccioni, MarianaCANCER IMMUNOTHERAPYCD103+ CDC1DSRNA MIMETICSTLR3TUMOR-INFILTRATEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3An important challenge in cancer immunotherapy is to expand the number of patients that benefit from immune checkpoint inhibitors (CI), a fact that has been related to the pre-existence of an efficient antitumor immune response. Different strategies are being proposed to promote tumor immunity and to be used in combined therapies with CI. Recently, we reported that intratumoral administration of naked poly A:U, a dsRNA mimetic empirically used in early clinical trials with some success, delays tumor growth and prolongs mice survival in several murine cancer models. Here, we show that CD103+ cDC1 and, to a much lesser extent CD11b+ cDC2, are the only populations expressing TLR3 at the tumor site, and consequently could be potential targets of poly A:U. Upon poly A:U administration these cells become activated and elicit profound changes in the composition of the tumor immune infiltrate, switching the immune suppressive tumor environment to anti-tumor immunity. The sole administration of naked poly A:U promotes striking changes within the lymphoid compartment, with all the anti-tumoral parameters being enhanced: a higher frequency of CD8+ Granzyme B+ T cells, (lower Treg/CD8+ ratio) and an important expansion of tumor-antigen specific CD8+ T cells. Also, PD1/PDL1 showed an increased expression indicating that neutralization of this axis could be exploited in combination with poly A:U. Our results shed new light to promote further assays in this dsRNA mimetic to the clinical field.Fil: Roselli, Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Araya, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Núñez, Nicolás. Institute Of Experimental Immunology; Suiza. Universitat Zurich; SuizaFil: Gatti, Gerardo Alberto. Fundación Para El Progreso de la Medicina; ArgentinaFil: Graziano, Francesca. Instituto Curie; FranciaFil: Sedlik, Christine. Instituto Curie; FranciaFil: Benaroch, Philippe. Instituto Curie; FranciaFil: Piaggio, Eliane. Instituto Curie; FranciaFil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFrontiers Media S.A.2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/129076Roselli, Emiliano; Araya, Paula; Núñez, Nicolás; Gatti, Gerardo Alberto; Graziano, Francesca; et al.; TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity; Frontiers Media S.A.; Frontiers in Immunology; 10; 3-2019; 1-141664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.00503/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00503info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:10:53Zoai:ri.conicet.gov.ar:11336/129076instacron: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:34982025-10-22 12:10:54.259CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
title TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
spellingShingle TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
Roselli, Emiliano
CANCER IMMUNOTHERAPY
CD103+ CDC1
DSRNA MIMETICS
TLR3
TUMOR-INFILTRATE
title_short TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
title_full TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
title_fullStr TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
title_full_unstemmed TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
title_sort TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity
dc.creator.none.fl_str_mv Roselli, Emiliano
Araya, Paula
Núñez, Nicolás
Gatti, Gerardo Alberto
Graziano, Francesca
Sedlik, Christine
Benaroch, Philippe
Piaggio, Eliane
Maccioni, Mariana
author Roselli, Emiliano
author_facet Roselli, Emiliano
Araya, Paula
Núñez, Nicolás
Gatti, Gerardo Alberto
Graziano, Francesca
Sedlik, Christine
Benaroch, Philippe
Piaggio, Eliane
Maccioni, Mariana
author_role author
author2 Araya, Paula
Núñez, Nicolás
Gatti, Gerardo Alberto
Graziano, Francesca
Sedlik, Christine
Benaroch, Philippe
Piaggio, Eliane
Maccioni, Mariana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CANCER IMMUNOTHERAPY
CD103+ CDC1
DSRNA MIMETICS
TLR3
TUMOR-INFILTRATE
topic CANCER IMMUNOTHERAPY
CD103+ CDC1
DSRNA MIMETICS
TLR3
TUMOR-INFILTRATE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv An important challenge in cancer immunotherapy is to expand the number of patients that benefit from immune checkpoint inhibitors (CI), a fact that has been related to the pre-existence of an efficient antitumor immune response. Different strategies are being proposed to promote tumor immunity and to be used in combined therapies with CI. Recently, we reported that intratumoral administration of naked poly A:U, a dsRNA mimetic empirically used in early clinical trials with some success, delays tumor growth and prolongs mice survival in several murine cancer models. Here, we show that CD103+ cDC1 and, to a much lesser extent CD11b+ cDC2, are the only populations expressing TLR3 at the tumor site, and consequently could be potential targets of poly A:U. Upon poly A:U administration these cells become activated and elicit profound changes in the composition of the tumor immune infiltrate, switching the immune suppressive tumor environment to anti-tumor immunity. The sole administration of naked poly A:U promotes striking changes within the lymphoid compartment, with all the anti-tumoral parameters being enhanced: a higher frequency of CD8+ Granzyme B+ T cells, (lower Treg/CD8+ ratio) and an important expansion of tumor-antigen specific CD8+ T cells. Also, PD1/PDL1 showed an increased expression indicating that neutralization of this axis could be exploited in combination with poly A:U. Our results shed new light to promote further assays in this dsRNA mimetic to the clinical field.
Fil: Roselli, Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Araya, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Núñez, Nicolás. Institute Of Experimental Immunology; Suiza. Universitat Zurich; Suiza
Fil: Gatti, Gerardo Alberto. Fundación Para El Progreso de la Medicina; Argentina
Fil: Graziano, Francesca. Instituto Curie; Francia
Fil: Sedlik, Christine. Instituto Curie; Francia
Fil: Benaroch, Philippe. Instituto Curie; Francia
Fil: Piaggio, Eliane. Instituto Curie; Francia
Fil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description An important challenge in cancer immunotherapy is to expand the number of patients that benefit from immune checkpoint inhibitors (CI), a fact that has been related to the pre-existence of an efficient antitumor immune response. Different strategies are being proposed to promote tumor immunity and to be used in combined therapies with CI. Recently, we reported that intratumoral administration of naked poly A:U, a dsRNA mimetic empirically used in early clinical trials with some success, delays tumor growth and prolongs mice survival in several murine cancer models. Here, we show that CD103+ cDC1 and, to a much lesser extent CD11b+ cDC2, are the only populations expressing TLR3 at the tumor site, and consequently could be potential targets of poly A:U. Upon poly A:U administration these cells become activated and elicit profound changes in the composition of the tumor immune infiltrate, switching the immune suppressive tumor environment to anti-tumor immunity. The sole administration of naked poly A:U promotes striking changes within the lymphoid compartment, with all the anti-tumoral parameters being enhanced: a higher frequency of CD8+ Granzyme B+ T cells, (lower Treg/CD8+ ratio) and an important expansion of tumor-antigen specific CD8+ T cells. Also, PD1/PDL1 showed an increased expression indicating that neutralization of this axis could be exploited in combination with poly A:U. Our results shed new light to promote further assays in this dsRNA mimetic to the clinical field.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
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/11336/129076
Roselli, Emiliano; Araya, Paula; Núñez, Nicolás; Gatti, Gerardo Alberto; Graziano, Francesca; et al.; TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity; Frontiers Media S.A.; Frontiers in Immunology; 10; 3-2019; 1-14
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/129076
identifier_str_mv Roselli, Emiliano; Araya, Paula; Núñez, Nicolás; Gatti, Gerardo Alberto; Graziano, Francesca; et al.; TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity; Frontiers Media S.A.; Frontiers in Immunology; 10; 3-2019; 1-14
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.00503/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00503
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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 12.982451

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