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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/129076
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:38:40Zoai: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:34982025-09-29 10:38:41.225CONICET 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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844614410460463104 |
score |
13.070432 |