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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2025
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| Mynediad Ar-lein: | https://hdl.handle.net/20.500.12008/50801 |
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Dim Tagiau, Byddwch y cyntaf i dagio'r cofnod hwn!
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| _version_ | 1868890089077080064 |
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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 |
| format | article |
| id | anni_6cb920d140b65535befa7cb4e30cd272 |
| 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 |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/50801 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| 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 |