STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors

Autores
Woo, Seng Ryong; Fuertes, Mercedes Beatriz; Corrales, Leticia; Spranger, Stefani; Furdyna, Michael J.; Leung, Michael Y. K.; Duggan, Ryan; Wang, Ying; Barber, Glen N.; Fitzgerald, Katherine A.; Alegre, Maria luisa; Gajewski, Thomas F.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8+ T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-β production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-β production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy.
Fil: Woo, Seng Ryong . University Of Chicago; Estados Unidos
Fil: Fuertes, Mercedes Beatriz. University Of Chicago; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Corrales, Leticia . University Of Chicago; Estados Unidos
Fil: Spranger, Stefani . University Of Chicago; Estados Unidos
Fil: Furdyna, Michael J. . University Of Chicago; Estados Unidos
Fil: Leung, Michael Y. K.. University Of Chicago; Estados Unidos
Fil: Duggan, Ryan . University Of Chicago; Estados Unidos
Fil: Wang, Ying . University Of Chicago; Estados Unidos
Fil: Barber, Glen N. . University Of Miami; Estados Unidos
Fil: Fitzgerald, Katherine A.. University Of Massachussets; Estados Unidos
Fil: Alegre, Maria luisa. University Of Chicago; Estados Unidos
Fil: Gajewski, Thomas F. . University Of Chicago; Estados Unidos
Materia
STING
DNA
TUMOR
IMMUNITY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6683
Acceder
id CONICETDig_cf81298c4a4297daaea094bc915861e9
oai_identifier_str oai:ri.conicet.gov.ar:11336/6683
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumorsWoo, Seng Ryong Fuertes, Mercedes BeatrizCorrales, Leticia Spranger, Stefani Furdyna, Michael J. Leung, Michael Y. K.Duggan, Ryan Wang, Ying Barber, Glen N. Fitzgerald, Katherine A.Alegre, Maria luisaGajewski, Thomas F. STINGDNATUMORIMMUNITYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8+ T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-β production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-β production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy.Fil: Woo, Seng Ryong . University Of Chicago; Estados UnidosFil: Fuertes, Mercedes Beatriz. University Of Chicago; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Corrales, Leticia . University Of Chicago; Estados UnidosFil: Spranger, Stefani . University Of Chicago; Estados UnidosFil: Furdyna, Michael J. . University Of Chicago; Estados UnidosFil: Leung, Michael Y. K.. University Of Chicago; Estados UnidosFil: Duggan, Ryan . University Of Chicago; Estados UnidosFil: Wang, Ying . University Of Chicago; Estados UnidosFil: Barber, Glen N. . University Of Miami; Estados UnidosFil: Fitzgerald, Katherine A.. University Of Massachussets; Estados UnidosFil: Alegre, Maria luisa. University Of Chicago; Estados UnidosFil: Gajewski, Thomas F. . University Of Chicago; Estados UnidosCell Press2014-11-20info: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/11336/6683Woo, Seng Ryong ; Fuertes, Mercedes Beatriz; Corrales, Leticia ; Spranger, Stefani ; Furdyna, Michael J. ; et al.; STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors; Cell Press; Immunity; 41; 5; 20-11-2014; 830-8421074-76131097-4180enginfo:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384884/info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.immuni.2014.10.017info:eu-repo/semantics/altIdentifier/pmid/PMC4384884info:eu-repo/semantics/altIdentifier/purl/http://www.sciencedirect.com/science/article/pii/S1074761314003938info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:05:11Zoai:ri.conicet.gov.ar:11336/6683instacron: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 15:05:11.889CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
title STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
spellingShingle STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
Woo, Seng Ryong
STING
DNA
TUMOR
IMMUNITY
title_short STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
title_full STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
title_fullStr STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
title_full_unstemmed STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
title_sort STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors
dc.creator.none.fl_str_mv Woo, Seng Ryong
Fuertes, Mercedes Beatriz
Corrales, Leticia
Spranger, Stefani
Furdyna, Michael J.
Leung, Michael Y. K.
Duggan, Ryan
Wang, Ying
Barber, Glen N.
Fitzgerald, Katherine A.
Alegre, Maria luisa
Gajewski, Thomas F.
author Woo, Seng Ryong
author_facet Woo, Seng Ryong
Fuertes, Mercedes Beatriz
Corrales, Leticia
Spranger, Stefani
Furdyna, Michael J.
Leung, Michael Y. K.
Duggan, Ryan
Wang, Ying
Barber, Glen N.
Fitzgerald, Katherine A.
Alegre, Maria luisa
Gajewski, Thomas F.
author_role author
author2 Fuertes, Mercedes Beatriz
Corrales, Leticia
Spranger, Stefani
Furdyna, Michael J.
Leung, Michael Y. K.
Duggan, Ryan
Wang, Ying
Barber, Glen N.
Fitzgerald, Katherine A.
Alegre, Maria luisa
Gajewski, Thomas F.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv STING
DNA
TUMOR
IMMUNITY
topic STING
DNA
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 Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8+ T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-β production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-β production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy.
Fil: Woo, Seng Ryong . University Of Chicago; Estados Unidos
Fil: Fuertes, Mercedes Beatriz. University Of Chicago; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Corrales, Leticia . University Of Chicago; Estados Unidos
Fil: Spranger, Stefani . University Of Chicago; Estados Unidos
Fil: Furdyna, Michael J. . University Of Chicago; Estados Unidos
Fil: Leung, Michael Y. K.. University Of Chicago; Estados Unidos
Fil: Duggan, Ryan . University Of Chicago; Estados Unidos
Fil: Wang, Ying . University Of Chicago; Estados Unidos
Fil: Barber, Glen N. . University Of Miami; Estados Unidos
Fil: Fitzgerald, Katherine A.. University Of Massachussets; Estados Unidos
Fil: Alegre, Maria luisa. University Of Chicago; Estados Unidos
Fil: Gajewski, Thomas F. . University Of Chicago; Estados Unidos
description Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8+ T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-β production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-β production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy.
publishDate 2014
dc.date.none.fl_str_mv 2014-11-20
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/11336/6683
Woo, Seng Ryong ; Fuertes, Mercedes Beatriz; Corrales, Leticia ; Spranger, Stefani ; Furdyna, Michael J. ; et al.; STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors; Cell Press; Immunity; 41; 5; 20-11-2014; 830-842
1074-7613
1097-4180
url http://hdl.handle.net/11336/6683
identifier_str_mv Woo, Seng Ryong ; Fuertes, Mercedes Beatriz; Corrales, Leticia ; Spranger, Stefani ; Furdyna, Michael J. ; et al.; STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors; Cell Press; Immunity; 41; 5; 20-11-2014; 830-842
1074-7613
1097-4180
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384884/
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.immuni.2014.10.017
info:eu-repo/semantics/altIdentifier/pmid/PMC4384884
info:eu-repo/semantics/altIdentifier/purl/http://www.sciencedirect.com/science/article/pii/S1074761314003938
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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
_version_ 1846083194508541952
score 13.216834

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