Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy

The current understanding of innate immune memory encompasses both trained immunity and immune tolerance, where cells can exhibit enhanced responsiveness or immune paralysis upon subsequent stimuli, respectively. Various agents induce either of these responses, including b-glucan, Leishmania, BCG an...

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Prif Awdur: Chilibroste, Sofía (author)
Awduron Eraill: dos Santos, Jéssica C. (author), Mónaco, Amy (author), Joosten, Leo A. B. (author), Moreno, María (author), Chabalgoity, José A. (author)
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Iaith:Saesneg
Cyhoeddwyd: 2025
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Mynediad Ar-lein:https://hdl.handle.net/20.500.12008/50801
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author Chilibroste, Sofía
author2 dos Santos, Jéssica C.
Mónaco, Amy
Joosten, Leo A. B.
Moreno, María
Chabalgoity, José A.
author2_role author
author
author
author
author
author_browse Chabalgoity, José A.
Chilibroste, Sofía
Joosten, Leo A. B.
Moreno, María
Mónaco, Amy
dos Santos, Jéssica C.
author_facet Chilibroste, Sofía
dos Santos, Jéssica C.
Mónaco, Amy
Joosten, Leo A. B.
Moreno, María
Chabalgoity, José A.
author_role author
collection COLIBRI
dc.contributor.none.fl_str_mv Chilibroste Sofía, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo Biotecnológico
dos Santos Jéssica C., Radboud University Medical Center (Países Bajos). Department of Internal Medicine
Mónaco Amy, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo Biotecnológico
Joosten Leo A. B., Radboud University Medical Center (Países Bajos). Department of Internal Medicine
Moreno María, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo Biotecnológico
Chabalgoity José A., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo Biotecnológico
dc.creator.none.fl_str_mv Chilibroste, Sofía
dos Santos, Jéssica C.
Mónaco, Amy
Joosten, Leo A. B.
Moreno, María
Chabalgoity, José A.
dc.date.none.fl_str_mv 2025-07-28T20:43:21Z
2025-07-28T20:43:21Z
2025
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv CHILIBROSTE, S., DOS SANTOS, JC., MÓNACO, A., y otros. Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy. Front. Immunol [en línea] 2025, 16. DOI: 10.3389/fimmu.2025.1535131
https://hdl.handle.net/20.500.12008/50801
10.3389/fimmu.2025.1535131
dc.language.none.fl_str_mv en
eng
dc.relation.none.fl_str_mv Front. Immunol. 16, 2025
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Licencia Creative Commons Atribución (CC - By 4.0)
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.none.fl_str_mv Salmonella
Innate immune memory
Trained immunity
Tolerance
Cancer immunotherapies
Anti-tumor Immunity
dc.title.none.fl_str_mv Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
dc.type.none.fl_str_mv Artículo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
description The current understanding of innate immune memory encompasses both trained immunity and immune tolerance, where cells can exhibit enhanced responsiveness or immune paralysis upon subsequent stimuli, respectively. Various agents induce either of these responses, including b-glucan, Leishmania, BCG and LPS. BCG is a clinically approved immunotherapy for bladder cancer and BCG-induced trained immunity is important in driving antitumor adaptive immunity. Salmonella also shows promise in cancer treatment, eliciting potent anti-tumor immune responses, but with transitory effects. This led us to investigate whether Salmonella LVR01, like BCG, triggers trained immunity and its impact on anti-tumor responses. Herein, we report that Salmonella induces an enhanced response in bone marrow cells, characterized by a robust cytokine response upon a second stimulus, in a fashion that resembles trained immunity. Coherently with that, Salmonella administration induces enhanced responsiveness to a tumor implanted later in time, resulting in slow tumor growth and extended survival. However, in vitro stimulation of human monocytes and murine bone-marrow derived myeloid-enriched cells with Salmonella results in decreased production of cytokines resembling immune paralysis. Overall, our results suggest that Salmonella LVR01 induces enhanced responses of innate immune memory, as well as paralysis on monocytes. These two antagonistic effects could be the basis of the transitory effect of Salmonella treatment and suggest that further investigation on these phenomena could shed light on how to improve Salmonella-based immunotherapies for cancer.
eu_rights_str_mv openAccess
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identifier_str_mv CHILIBROSTE, S., DOS SANTOS, JC., MÓNACO, A., y otros. Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy. Front. Immunol [en línea] 2025, 16. DOI: 10.3389/fimmu.2025.1535131
10.3389/fimmu.2025.1535131
instacron_str Universidad de la República
institution Universidad de la República
instname_str Universidad de la República
language eng
language_invalid_str_mv en
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oai_identifier_str oai:colibri.udelar.edu.uy:20.500.12008/50801
publishDate 2025
publishDateSort 2025
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rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacyChilibroste, Sofíados Santos, Jéssica C.Mónaco, AmyJoosten, Leo A. B.Moreno, MaríaChabalgoity, José A.SalmonellaInnate immune memoryTrained immunityToleranceCancer immunotherapiesAnti-tumor ImmunityThe current understanding of innate immune memory encompasses both trained immunity and immune tolerance, where cells can exhibit enhanced responsiveness or immune paralysis upon subsequent stimuli, respectively. Various agents induce either of these responses, including b-glucan, Leishmania, BCG and LPS. BCG is a clinically approved immunotherapy for bladder cancer and BCG-induced trained immunity is important in driving antitumor adaptive immunity. Salmonella also shows promise in cancer treatment, eliciting potent anti-tumor immune responses, but with transitory effects. This led us to investigate whether Salmonella LVR01, like BCG, triggers trained immunity and its impact on anti-tumor responses. Herein, we report that Salmonella induces an enhanced response in bone marrow cells, characterized by a robust cytokine response upon a second stimulus, in a fashion that resembles trained immunity. Coherently with that, Salmonella administration induces enhanced responsiveness to a tumor implanted later in time, resulting in slow tumor growth and extended survival. However, in vitro stimulation of human monocytes and murine bone-marrow derived myeloid-enriched cells with Salmonella results in decreased production of cytokines resembling immune paralysis. Overall, our results suggest that Salmonella LVR01 induces enhanced responses of innate immune memory, as well as paralysis on monocytes. These two antagonistic effects could be the basis of the transitory effect of Salmonella treatment and suggest that further investigation on these phenomena could shed light on how to improve Salmonella-based immunotherapies for cancer.Agencia Nacional de Investigación e Innovación (ANII)Comisión Sectorial de Investigación Científica (CSIC)Programa de Posgrado en Biotecnología (UdelaR)Chilibroste Sofía, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo Biotecnológicodos Santos Jéssica C., Radboud University Medical Center (Países Bajos). Department of Internal MedicineMónaco Amy, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo BiotecnológicoJoosten Leo A. B., Radboud University Medical Center (Países Bajos). Department of Internal MedicineMoreno María, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo BiotecnológicoChabalgoity José A., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Desarrollo Biotecnológico2025-07-28T20:43:21Z2025-07-28T20:43:21Z2025Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfCHILIBROSTE, S., DOS SANTOS, JC., MÓNACO, A., y otros. Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy. Front. Immunol [en línea] 2025, 16. DOI: 10.3389/fimmu.2025.1535131https://hdl.handle.net/20.500.12008/5080110.3389/fimmu.2025.1535131reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengFront. Immunol. 16, 2025Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/508012026-04-14T10:37:02Z
spellingShingle Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
Chilibroste, Sofía
Salmonella
Innate immune memory
Trained immunity
Tolerance
Cancer immunotherapies
Anti-tumor Immunity
status_str publishedVersion
title Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
title_full Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
title_fullStr Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
title_full_unstemmed Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
title_short Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
title_sort Salmonella LVR01 triggers antagonistic two-armed innate immune memory that impacts on antitumor efficacy
topic Salmonella
Innate immune memory
Trained immunity
Tolerance
Cancer immunotherapies
Anti-tumor Immunity
url https://hdl.handle.net/20.500.12008/50801