IL-23 stabilizes an effector Treg cell program in the tumor microenvironment

Autores
Wertheimer, Tobias; Zwicky, Pascale; Rindlisbacher, Lukas; Sparano, Colin; Vermeer, Marijne; de Melo, Bruno Marcel Silva; Haftmann, Claudia; Rückert, Tamina; Sethi, Aakriti; Schärli, Stefanie; Huber, Anna; Ingelfinger, Florian; Xu, Caroline; Kim, Daehong; Häne, Philipp; Fonseca da Silva, André; Muschaweckh, Andreas; Núñez, Nicolás; Krishnarajah, Sinduya; Köhler, Natalie; Zeiser, Robert; Oukka, Mohamed; Korn, Thomas; Tugues, Sonia; Becher, Burkhard
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (Treg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in Treg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector Treg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.
Fil: Wertheimer, Tobias. Universitat Zurich; Suiza
Fil: Zwicky, Pascale. Universitat Zurich; Suiza
Fil: Rindlisbacher, Lukas. Universitat Zurich; Suiza
Fil: Sparano, Colin. Universitat Zurich; Suiza
Fil: Vermeer, Marijne. Universitat Zurich; Suiza
Fil: de Melo, Bruno Marcel Silva. Universitat Zurich; Suiza. Universidade de Sao Paulo; Brasil
Fil: Haftmann, Claudia. Universitat Zurich; Suiza
Fil: Rückert, Tamina. Albert Ludwigs University of Freiburg; Alemania
Fil: Sethi, Aakriti. Universitat Zurich; Suiza
Fil: Schärli, Stefanie. Universitat Zurich; Suiza
Fil: Huber, Anna. Universitat Zurich; Suiza
Fil: Ingelfinger, Florian. Universitat Zurich; Suiza
Fil: Xu, Caroline. Universitat Zurich; Suiza
Fil: Kim, Daehong. Universitat Zurich; Suiza
Fil: Häne, Philipp. Universitat Zurich; Suiza
Fil: Fonseca da Silva, André. Universitat Zurich; Suiza
Fil: Muschaweckh, Andreas. Universitat Technical Zu Munich; Alemania
Fil: Núñez, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universitat Zurich; Suiza
Fil: Krishnarajah, Sinduya. Universitat Zurich; Suiza
Fil: Köhler, Natalie. Albert Ludwigs University of Freiburg; Alemania
Fil: Zeiser, Robert. Albert Ludwigs University of Freiburg; Alemania
Fil: Oukka, Mohamed. University of Washington; Estados Unidos
Fil: Korn, Thomas. Universitat Technical Zu Munich; Alemania
Fil: Tugues, Sonia. Universitat Zurich; Suiza
Fil: Becher, Burkhard. Universitat Zurich; Suiza
Materia
IL23R
Treg
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:11336/257208
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/257208
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling IL-23 stabilizes an effector Treg cell program in the tumor microenvironmentWertheimer, TobiasZwicky, PascaleRindlisbacher, LukasSparano, ColinVermeer, Marijnede Melo, Bruno Marcel SilvaHaftmann, ClaudiaRückert, TaminaSethi, AakritiSchärli, StefanieHuber, AnnaIngelfinger, FlorianXu, CarolineKim, DaehongHäne, PhilippFonseca da Silva, AndréMuschaweckh, AndreasNúñez, NicolásKrishnarajah, SinduyaKöhler, NatalieZeiser, RobertOukka, MohamedKorn, ThomasTugues, SoniaBecher, BurkhardIL23RTreghttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (Treg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in Treg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector Treg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.Fil: Wertheimer, Tobias. Universitat Zurich; SuizaFil: Zwicky, Pascale. Universitat Zurich; SuizaFil: Rindlisbacher, Lukas. Universitat Zurich; SuizaFil: Sparano, Colin. Universitat Zurich; SuizaFil: Vermeer, Marijne. Universitat Zurich; SuizaFil: de Melo, Bruno Marcel Silva. Universitat Zurich; Suiza. Universidade de Sao Paulo; BrasilFil: Haftmann, Claudia. Universitat Zurich; SuizaFil: Rückert, Tamina. Albert Ludwigs University of Freiburg; AlemaniaFil: Sethi, Aakriti. Universitat Zurich; SuizaFil: Schärli, Stefanie. Universitat Zurich; SuizaFil: Huber, Anna. Universitat Zurich; SuizaFil: Ingelfinger, Florian. Universitat Zurich; SuizaFil: Xu, Caroline. Universitat Zurich; SuizaFil: Kim, Daehong. Universitat Zurich; SuizaFil: Häne, Philipp. Universitat Zurich; SuizaFil: Fonseca da Silva, André. Universitat Zurich; SuizaFil: Muschaweckh, Andreas. Universitat Technical Zu Munich; AlemaniaFil: Núñez, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universitat Zurich; SuizaFil: Krishnarajah, Sinduya. Universitat Zurich; SuizaFil: Köhler, Natalie. Albert Ludwigs University of Freiburg; AlemaniaFil: Zeiser, Robert. Albert Ludwigs University of Freiburg; AlemaniaFil: Oukka, Mohamed. University of Washington; Estados UnidosFil: Korn, Thomas. Universitat Technical Zu Munich; AlemaniaFil: Tugues, Sonia. Universitat Zurich; SuizaFil: Becher, Burkhard. Universitat Zurich; SuizaNature Publishing Group2024-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/257208Wertheimer, Tobias; Zwicky, Pascale; Rindlisbacher, Lukas; Sparano, Colin; Vermeer, Marijne; et al.; IL-23 stabilizes an effector Treg cell program in the tumor microenvironment; Nature Publishing Group; Nature Immunology (print); 25; 3; 2-2024; 512-5241529-2916CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41590-024-01755-7info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41590-024-01755-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:29:03Zoai:ri.conicet.gov.ar:11336/257208instacron: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 15:29:03.348CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
title IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
spellingShingle IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
Wertheimer, Tobias
IL23R
Treg
title_short IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
title_full IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
title_fullStr IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
title_full_unstemmed IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
title_sort IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
dc.creator.none.fl_str_mv Wertheimer, Tobias
Zwicky, Pascale
Rindlisbacher, Lukas
Sparano, Colin
Vermeer, Marijne
de Melo, Bruno Marcel Silva
Haftmann, Claudia
Rückert, Tamina
Sethi, Aakriti
Schärli, Stefanie
Huber, Anna
Ingelfinger, Florian
Xu, Caroline
Kim, Daehong
Häne, Philipp
Fonseca da Silva, André
Muschaweckh, Andreas
Núñez, Nicolás
Krishnarajah, Sinduya
Köhler, Natalie
Zeiser, Robert
Oukka, Mohamed
Korn, Thomas
Tugues, Sonia
Becher, Burkhard
author Wertheimer, Tobias
author_facet Wertheimer, Tobias
Zwicky, Pascale
Rindlisbacher, Lukas
Sparano, Colin
Vermeer, Marijne
de Melo, Bruno Marcel Silva
Haftmann, Claudia
Rückert, Tamina
Sethi, Aakriti
Schärli, Stefanie
Huber, Anna
Ingelfinger, Florian
Xu, Caroline
Kim, Daehong
Häne, Philipp
Fonseca da Silva, André
Muschaweckh, Andreas
Núñez, Nicolás
Krishnarajah, Sinduya
Köhler, Natalie
Zeiser, Robert
Oukka, Mohamed
Korn, Thomas
Tugues, Sonia
Becher, Burkhard
author_role author
author2 Zwicky, Pascale
Rindlisbacher, Lukas
Sparano, Colin
Vermeer, Marijne
de Melo, Bruno Marcel Silva
Haftmann, Claudia
Rückert, Tamina
Sethi, Aakriti
Schärli, Stefanie
Huber, Anna
Ingelfinger, Florian
Xu, Caroline
Kim, Daehong
Häne, Philipp
Fonseca da Silva, André
Muschaweckh, Andreas
Núñez, Nicolás
Krishnarajah, Sinduya
Köhler, Natalie
Zeiser, Robert
Oukka, Mohamed
Korn, Thomas
Tugues, Sonia
Becher, Burkhard
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv IL23R
Treg
topic IL23R
Treg
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (Treg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in Treg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector Treg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.
Fil: Wertheimer, Tobias. Universitat Zurich; Suiza
Fil: Zwicky, Pascale. Universitat Zurich; Suiza
Fil: Rindlisbacher, Lukas. Universitat Zurich; Suiza
Fil: Sparano, Colin. Universitat Zurich; Suiza
Fil: Vermeer, Marijne. Universitat Zurich; Suiza
Fil: de Melo, Bruno Marcel Silva. Universitat Zurich; Suiza. Universidade de Sao Paulo; Brasil
Fil: Haftmann, Claudia. Universitat Zurich; Suiza
Fil: Rückert, Tamina. Albert Ludwigs University of Freiburg; Alemania
Fil: Sethi, Aakriti. Universitat Zurich; Suiza
Fil: Schärli, Stefanie. Universitat Zurich; Suiza
Fil: Huber, Anna. Universitat Zurich; Suiza
Fil: Ingelfinger, Florian. Universitat Zurich; Suiza
Fil: Xu, Caroline. Universitat Zurich; Suiza
Fil: Kim, Daehong. Universitat Zurich; Suiza
Fil: Häne, Philipp. Universitat Zurich; Suiza
Fil: Fonseca da Silva, André. Universitat Zurich; Suiza
Fil: Muschaweckh, Andreas. Universitat Technical Zu Munich; Alemania
Fil: Núñez, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universitat Zurich; Suiza
Fil: Krishnarajah, Sinduya. Universitat Zurich; Suiza
Fil: Köhler, Natalie. Albert Ludwigs University of Freiburg; Alemania
Fil: Zeiser, Robert. Albert Ludwigs University of Freiburg; Alemania
Fil: Oukka, Mohamed. University of Washington; Estados Unidos
Fil: Korn, Thomas. Universitat Technical Zu Munich; Alemania
Fil: Tugues, Sonia. Universitat Zurich; Suiza
Fil: Becher, Burkhard. Universitat Zurich; Suiza
description Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (Treg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in Treg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector Treg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.
publishDate 2024
dc.date.none.fl_str_mv 2024-02
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/11336/257208
Wertheimer, Tobias; Zwicky, Pascale; Rindlisbacher, Lukas; Sparano, Colin; Vermeer, Marijne; et al.; IL-23 stabilizes an effector Treg cell program in the tumor microenvironment; Nature Publishing Group; Nature Immunology (print); 25; 3; 2-2024; 512-524
1529-2916
CONICET Digital
CONICET
url http://hdl.handle.net/11336/257208
identifier_str_mv Wertheimer, Tobias; Zwicky, Pascale; Rindlisbacher, Lukas; Sparano, Colin; Vermeer, Marijne; et al.; IL-23 stabilizes an effector Treg cell program in the tumor microenvironment; Nature Publishing Group; Nature Immunology (print); 25; 3; 2-2024; 512-524
1529-2916
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41590-024-01755-7
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41590-024-01755-7
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 13.22299

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