Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation

Autores
Rutkowski, Melanie R.; Stephen, Tom L.; Svoronos, Nikolaos; Allegrezza, Michael J.; Tesone, Amelia J.; Perales Puchalt, Alfredo; Brencicova, Eva; Escovar Fadul, Ximena; Nguyen, Jenny M.; Cadungog, Mark G.; Zhang, Rugang; Salatino, Mariana; Tchou, Julia; Rabinovich, Gabriel Adrián; Conejo Garcia, Jose R.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.
Fil: Rutkowski, Melanie R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Stephen, Tom L.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Svoronos, Nikolaos. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Allegrezza, Michael J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Tesone, Amelia J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Perales Puchalt, Alfredo. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Brencicova, Eva. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Escovar Fadul, Ximena. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Nguyen, Jenny M.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Cadungog, Mark G.. Christiana Care Health System. Helen F. Graham Cancer Center; Estados Unidos
Fil: Zhang, Rugang. The Wistar Institute. Gene Expression and Regulation Program; Estados Unidos
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Tchou, Julia. University of Pennsylvania; Estados Unidos
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Conejo Garcia, Jose R.. The Wistar Institute. Gene Expression and Regulation Program; Estados Unidos
Materia
Bacteria
Tlr5
Myeloid-Derived Suppresor Cells
Tumor
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:11336/22973
Acceder
id CONICETDig_19cf42a2c67af6551bcddb319cd25503
oai_identifier_str oai:ri.conicet.gov.ar:11336/22973
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammationRutkowski, Melanie R.Stephen, Tom L.Svoronos, NikolaosAllegrezza, Michael J.Tesone, Amelia J.Perales Puchalt, AlfredoBrencicova, EvaEscovar Fadul, XimenaNguyen, Jenny M.Cadungog, Mark G.Zhang, RugangSalatino, MarianaTchou, JuliaRabinovich, Gabriel AdriánConejo Garcia, Jose R.BacteriaTlr5Myeloid-Derived Suppresor CellsTumorhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.Fil: Rutkowski, Melanie R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Stephen, Tom L.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Svoronos, Nikolaos. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Allegrezza, Michael J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Tesone, Amelia J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Perales Puchalt, Alfredo. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Brencicova, Eva. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Escovar Fadul, Ximena. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Nguyen, Jenny M.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Cadungog, Mark G.. Christiana Care Health System. Helen F. Graham Cancer Center; Estados UnidosFil: Zhang, Rugang. The Wistar Institute. Gene Expression and Regulation Program; Estados UnidosFil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Tchou, Julia. University of Pennsylvania; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Conejo Garcia, Jose R.. The Wistar Institute. Gene Expression and Regulation Program; Estados UnidosCell Press2015-01-12info: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/11336/22973Rutkowski, Melanie R.; Stephen, Tom L.; Svoronos, Nikolaos; Allegrezza, Michael J.; Tesone, Amelia J.; et al.; Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation; Cell Press; Cancer Cell; 27; 1; 12-1-2015; 27-401535-61081878-3686CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.cell.com/cancer-cell/fulltext/S1535-6108(14)00460-7info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ccell.2014.11.009info:eu-repo/semantics/altIdentifier/pmid/25533336info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293269/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:16:37Zoai:ri.conicet.gov.ar:11336/22973instacron: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 12:16:38.2CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
title Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
spellingShingle Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
Rutkowski, Melanie R.
Bacteria
Tlr5
Myeloid-Derived Suppresor Cells
Tumor
title_short Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
title_full Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
title_fullStr Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
title_full_unstemmed Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
title_sort Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation
dc.creator.none.fl_str_mv Rutkowski, Melanie R.
Stephen, Tom L.
Svoronos, Nikolaos
Allegrezza, Michael J.
Tesone, Amelia J.
Perales Puchalt, Alfredo
Brencicova, Eva
Escovar Fadul, Ximena
Nguyen, Jenny M.
Cadungog, Mark G.
Zhang, Rugang
Salatino, Mariana
Tchou, Julia
Rabinovich, Gabriel Adrián
Conejo Garcia, Jose R.
author Rutkowski, Melanie R.
author_facet Rutkowski, Melanie R.
Stephen, Tom L.
Svoronos, Nikolaos
Allegrezza, Michael J.
Tesone, Amelia J.
Perales Puchalt, Alfredo
Brencicova, Eva
Escovar Fadul, Ximena
Nguyen, Jenny M.
Cadungog, Mark G.
Zhang, Rugang
Salatino, Mariana
Tchou, Julia
Rabinovich, Gabriel Adrián
Conejo Garcia, Jose R.
author_role author
author2 Stephen, Tom L.
Svoronos, Nikolaos
Allegrezza, Michael J.
Tesone, Amelia J.
Perales Puchalt, Alfredo
Brencicova, Eva
Escovar Fadul, Ximena
Nguyen, Jenny M.
Cadungog, Mark G.
Zhang, Rugang
Salatino, Mariana
Tchou, Julia
Rabinovich, Gabriel Adrián
Conejo Garcia, Jose R.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bacteria
Tlr5
Myeloid-Derived Suppresor Cells
Tumor
topic Bacteria
Tlr5
Myeloid-Derived Suppresor Cells
Tumor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.
Fil: Rutkowski, Melanie R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Stephen, Tom L.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Svoronos, Nikolaos. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Allegrezza, Michael J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Tesone, Amelia J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Perales Puchalt, Alfredo. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Brencicova, Eva. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Escovar Fadul, Ximena. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Nguyen, Jenny M.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unidos
Fil: Cadungog, Mark G.. Christiana Care Health System. Helen F. Graham Cancer Center; Estados Unidos
Fil: Zhang, Rugang. The Wistar Institute. Gene Expression and Regulation Program; Estados Unidos
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Tchou, Julia. University of Pennsylvania; Estados Unidos
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Conejo Garcia, Jose R.. The Wistar Institute. Gene Expression and Regulation Program; Estados Unidos
description The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.
publishDate 2015
dc.date.none.fl_str_mv 2015-01-12
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/11336/22973
Rutkowski, Melanie R.; Stephen, Tom L.; Svoronos, Nikolaos; Allegrezza, Michael J.; Tesone, Amelia J.; et al.; Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation; Cell Press; Cancer Cell; 27; 1; 12-1-2015; 27-40
1535-6108
1878-3686
CONICET Digital
CONICET
url http://hdl.handle.net/11336/22973
identifier_str_mv Rutkowski, Melanie R.; Stephen, Tom L.; Svoronos, Nikolaos; Allegrezza, Michael J.; Tesone, Amelia J.; et al.; Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation; Cell Press; Cancer Cell; 27; 1; 12-1-2015; 27-40
1535-6108
1878-3686
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/cancer-cell/fulltext/S1535-6108(14)00460-7
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ccell.2014.11.009
info:eu-repo/semantics/altIdentifier/pmid/25533336
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293269/
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 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_ 1846782587088928768
score 12.982451

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