Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control

Autores
Savid Frontera, Constanza; Viano, María Estefanía; Baez, Natalia Soledad; Lidon, Nicolás Leonel; Fontaine, Quentin; Young, Howard A.; Vimeux, Lene; Donnadieu, Emmanuel; Rodriguez Galan, Maria Cecilia
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Virtual memory CD8+ T cells (TVM) have been described as cells with a memory-like phenotype but without previous antigen (Ag) exposure. TVM cells have the ability to respond better to innate stimuli rather than by TCR engagement, producing large amounts of interferon gamma (IFNγ) after stimulation with interleukin (IL)-12 plus IL-18. As a result of the phenotypic similarity, TVM cells have been erroneously included in the central memory T cell subset for many years. However, they can now be discriminated via the CD49d receptor, which is up-regulated only on conventional memory T cells (TMEM) and effector T cells (TEFF) after specific cognate Ag recognition by a TCR. In this work we show that systemic expression of IL-12 plus IL-18 induced an alteration in the normal TVM vs TMEM/TEFF distribution in secondary lymphoid organs and a preferential enrichment of TVM cells in the melanoma (B16) and the pancreatic ductal adenocarcinoma (KPC) tumor models. Using our KPC bearing OT-I mouse model, we observed a significant increase in CD8+ T cell infiltrating the tumor islets after IL-12+IL-18 stimulation with a lower average speed when compared to those from control mice. This finding indicates a stronger interaction of T cells with tumor cells after cytokine stimulation. These results correlate with a significant reduction in tumor size in both tumor models in IL-12+IL-18-treated OT-I mice compared to control OT-I mice. Interestingly, the absence of IFNγ completely abolished the high antitumor capacity induced by IL-12+IL-18 expression, indicating an important role for these cytokines in early tumor growth control. Thus, our studies provide significant new information that indicates an important role of TVM cells in the immune response against cancer.
Fil: Savid Frontera, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Viano, María Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Baez, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Lidon, Nicolás Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Fontaine, Quentin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Young, Howard A.. No especifíca;
Fil: Vimeux, Lene. Centre National de la Recherche Scientifique; Francia
Fil: Donnadieu, Emmanuel. Centre National de la Recherche Scientifique; Francia
Fil: Rodriguez Galan, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
CANCER
IFNG
IL-12
IL-18
VIRTUAL MEMORY CD8+ T CELLS
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:11336/218050
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/218050
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth controlSavid Frontera, ConstanzaViano, María EstefaníaBaez, Natalia SoledadLidon, Nicolás LeonelFontaine, QuentinYoung, Howard A.Vimeux, LeneDonnadieu, EmmanuelRodriguez Galan, Maria CeciliaCANCERIFNGIL-12IL-18VIRTUAL MEMORY CD8+ T CELLShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Virtual memory CD8+ T cells (TVM) have been described as cells with a memory-like phenotype but without previous antigen (Ag) exposure. TVM cells have the ability to respond better to innate stimuli rather than by TCR engagement, producing large amounts of interferon gamma (IFNγ) after stimulation with interleukin (IL)-12 plus IL-18. As a result of the phenotypic similarity, TVM cells have been erroneously included in the central memory T cell subset for many years. However, they can now be discriminated via the CD49d receptor, which is up-regulated only on conventional memory T cells (TMEM) and effector T cells (TEFF) after specific cognate Ag recognition by a TCR. In this work we show that systemic expression of IL-12 plus IL-18 induced an alteration in the normal TVM vs TMEM/TEFF distribution in secondary lymphoid organs and a preferential enrichment of TVM cells in the melanoma (B16) and the pancreatic ductal adenocarcinoma (KPC) tumor models. Using our KPC bearing OT-I mouse model, we observed a significant increase in CD8+ T cell infiltrating the tumor islets after IL-12+IL-18 stimulation with a lower average speed when compared to those from control mice. This finding indicates a stronger interaction of T cells with tumor cells after cytokine stimulation. These results correlate with a significant reduction in tumor size in both tumor models in IL-12+IL-18-treated OT-I mice compared to control OT-I mice. Interestingly, the absence of IFNγ completely abolished the high antitumor capacity induced by IL-12+IL-18 expression, indicating an important role for these cytokines in early tumor growth control. Thus, our studies provide significant new information that indicates an important role of TVM cells in the immune response against cancer.Fil: Savid Frontera, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Viano, María Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Baez, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Lidon, Nicolás Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Fontaine, Quentin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Young, Howard A.. No especifíca;Fil: Vimeux, Lene. Centre National de la Recherche Scientifique; FranciaFil: Donnadieu, Emmanuel. Centre National de la Recherche Scientifique; FranciaFil: Rodriguez Galan, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFrontiers Media2022-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/218050Savid Frontera, Constanza; Viano, María Estefanía; Baez, Natalia Soledad; Lidon, Nicolás Leonel; Fontaine, Quentin; et al.; Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control; Frontiers Media; Frontiers in Immunology; 13; 10-2022; 1-181664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2022.971001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:11:27Zoai:ri.conicet.gov.ar:11336/218050instacron: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 11:11:27.763CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
title Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
spellingShingle Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
Savid Frontera, Constanza
CANCER
IFNG
IL-12
IL-18
VIRTUAL MEMORY CD8+ T CELLS
title_short Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
title_full Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
title_fullStr Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
title_full_unstemmed Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
title_sort Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control
dc.creator.none.fl_str_mv Savid Frontera, Constanza
Viano, María Estefanía
Baez, Natalia Soledad
Lidon, Nicolás Leonel
Fontaine, Quentin
Young, Howard A.
Vimeux, Lene
Donnadieu, Emmanuel
Rodriguez Galan, Maria Cecilia
author Savid Frontera, Constanza
author_facet Savid Frontera, Constanza
Viano, María Estefanía
Baez, Natalia Soledad
Lidon, Nicolás Leonel
Fontaine, Quentin
Young, Howard A.
Vimeux, Lene
Donnadieu, Emmanuel
Rodriguez Galan, Maria Cecilia
author_role author
author2 Viano, María Estefanía
Baez, Natalia Soledad
Lidon, Nicolás Leonel
Fontaine, Quentin
Young, Howard A.
Vimeux, Lene
Donnadieu, Emmanuel
Rodriguez Galan, Maria Cecilia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CANCER
IFNG
IL-12
IL-18
VIRTUAL MEMORY CD8+ T CELLS
topic CANCER
IFNG
IL-12
IL-18
VIRTUAL MEMORY CD8+ T CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Virtual memory CD8+ T cells (TVM) have been described as cells with a memory-like phenotype but without previous antigen (Ag) exposure. TVM cells have the ability to respond better to innate stimuli rather than by TCR engagement, producing large amounts of interferon gamma (IFNγ) after stimulation with interleukin (IL)-12 plus IL-18. As a result of the phenotypic similarity, TVM cells have been erroneously included in the central memory T cell subset for many years. However, they can now be discriminated via the CD49d receptor, which is up-regulated only on conventional memory T cells (TMEM) and effector T cells (TEFF) after specific cognate Ag recognition by a TCR. In this work we show that systemic expression of IL-12 plus IL-18 induced an alteration in the normal TVM vs TMEM/TEFF distribution in secondary lymphoid organs and a preferential enrichment of TVM cells in the melanoma (B16) and the pancreatic ductal adenocarcinoma (KPC) tumor models. Using our KPC bearing OT-I mouse model, we observed a significant increase in CD8+ T cell infiltrating the tumor islets after IL-12+IL-18 stimulation with a lower average speed when compared to those from control mice. This finding indicates a stronger interaction of T cells with tumor cells after cytokine stimulation. These results correlate with a significant reduction in tumor size in both tumor models in IL-12+IL-18-treated OT-I mice compared to control OT-I mice. Interestingly, the absence of IFNγ completely abolished the high antitumor capacity induced by IL-12+IL-18 expression, indicating an important role for these cytokines in early tumor growth control. Thus, our studies provide significant new information that indicates an important role of TVM cells in the immune response against cancer.
Fil: Savid Frontera, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Viano, María Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Baez, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Lidon, Nicolás Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Fontaine, Quentin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Young, Howard A.. No especifíca;
Fil: Vimeux, Lene. Centre National de la Recherche Scientifique; Francia
Fil: Donnadieu, Emmanuel. Centre National de la Recherche Scientifique; Francia
Fil: Rodriguez Galan, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Virtual memory CD8+ T cells (TVM) have been described as cells with a memory-like phenotype but without previous antigen (Ag) exposure. TVM cells have the ability to respond better to innate stimuli rather than by TCR engagement, producing large amounts of interferon gamma (IFNγ) after stimulation with interleukin (IL)-12 plus IL-18. As a result of the phenotypic similarity, TVM cells have been erroneously included in the central memory T cell subset for many years. However, they can now be discriminated via the CD49d receptor, which is up-regulated only on conventional memory T cells (TMEM) and effector T cells (TEFF) after specific cognate Ag recognition by a TCR. In this work we show that systemic expression of IL-12 plus IL-18 induced an alteration in the normal TVM vs TMEM/TEFF distribution in secondary lymphoid organs and a preferential enrichment of TVM cells in the melanoma (B16) and the pancreatic ductal adenocarcinoma (KPC) tumor models. Using our KPC bearing OT-I mouse model, we observed a significant increase in CD8+ T cell infiltrating the tumor islets after IL-12+IL-18 stimulation with a lower average speed when compared to those from control mice. This finding indicates a stronger interaction of T cells with tumor cells after cytokine stimulation. These results correlate with a significant reduction in tumor size in both tumor models in IL-12+IL-18-treated OT-I mice compared to control OT-I mice. Interestingly, the absence of IFNγ completely abolished the high antitumor capacity induced by IL-12+IL-18 expression, indicating an important role for these cytokines in early tumor growth control. Thus, our studies provide significant new information that indicates an important role of TVM cells in the immune response against cancer.
publishDate 2022
dc.date.none.fl_str_mv 2022-10
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/11336/218050
Savid Frontera, Constanza; Viano, María Estefanía; Baez, Natalia Soledad; Lidon, Nicolás Leonel; Fontaine, Quentin; et al.; Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control; Frontiers Media; Frontiers in Immunology; 13; 10-2022; 1-18
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/218050
identifier_str_mv Savid Frontera, Constanza; Viano, María Estefanía; Baez, Natalia Soledad; Lidon, Nicolás Leonel; Fontaine, Quentin; et al.; Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control; Frontiers Media; Frontiers in Immunology; 13; 10-2022; 1-18
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/doi/10.3389/fimmu.2022.971001
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
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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