Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination
Blocking antibodies against immunosuppressive molecules have shown promising results in cancer patients. However, there are not enough data to define those conditions dictating treatment efficacy. In this scenario, IL-10 is a cytokine with controversial effects on tumor growth. Thus, our aim was to...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/69048 |
| Acceso en línea: | https://hdl.handle.net/10171/69048 |
| Access Level: | acceso abierto |
| Palabra clave: | Adjuvant Antitumor immunity Blockade Dendritic cells Interleukin-10 Therapeutic vaccination |
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oai:dadun.unav.edu:10171/69048 |
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España |
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Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccinationLlopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20Aranda-Vega, F. (Fernando)|||/items/967c4675-0318-4d3c-97dc-b5b09026995fDiaz-Valdes, N. (Nancy)|||/items/c3f11da4-b858-4792-acb1-a373a5db9430Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270Infante-Varillas, S.F. (Stefany Fiorella)|||/items/e866cf80-70e9-40e9-ad96-f9e8c5179014Belsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0cSarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160AdjuvantAntitumor immunityBlockadeDendritic cellsInterleukin-10Therapeutic vaccinationBlocking antibodies against immunosuppressive molecules have shown promising results in cancer patients. However, there are not enough data to define those conditions dictating treatment efficacy. In this scenario, IL-10 is a cytokine with controversial effects on tumor growth. Thus, our aim was to characterize in which setting IL-10 blockade may potentiate the beneficial effects of a therapeutic vaccine In the IL-10-expressing B16-OVA and TC-1 P3 (A15) tumor models, therapeutic vaccination with tumor antigens plus the TLR7 ligand Imiquimod increased IL-10 production. Although blockade of IL-10 signal with anti-IL-10R antibodies did not inhibit tumor growth, when combined with vaccination it enhanced tumor rejection, associated with stronger innate and adaptive immune responses. Interestingly, a similar enhancement on immune responses was observed after simultaneous vaccination and IL-10 blockade in naive mice. However, when using vaccines containing as adjuvants the TLR3 ligand poly(I:C) or anti-CD40 agonistic antibodies, despite tumor IL-10 expression, anti-IL-10R antibodies did not provide any beneficial effect on tumor growth and antitumor immune responses. Of note, as opposed to Imiquimod, vaccination with this type of adjuvants did not induce IL-10 and correlated with a lack of in vitro IL-10 production by dendritic cells (DC). Finally, in B16-OVA-bearing mice, blockade of IL-10 during therapeutic vaccination with a multiple adjuvant combination (MAC) with potent immunostimulatory properties but still inducing IL-10 led to superior antitumor immunity and complete tumor rejection. These results suggest that for therapeutic antitumor vaccination, blockade of vaccine-induced IL-10 is more relevant than tumorassociated IL-10.Taylor & FrancisDadun. Depósito Académico Digital Universidad de Navarra20242024-02-1020152015-01-0120152015-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/69048reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/690482026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination |
| title |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination |
| spellingShingle |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination Llopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20 Adjuvant Antitumor immunity Blockade Dendritic cells Interleukin-10 Therapeutic vaccination |
| title_short |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination |
| title_full |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination |
| title_fullStr |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination |
| title_full_unstemmed |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination |
| title_sort |
Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination |
| dc.creator.none.fl_str_mv |
Llopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20 Aranda-Vega, F. (Fernando)|||/items/967c4675-0318-4d3c-97dc-b5b09026995f Diaz-Valdes, N. (Nancy)|||/items/c3f11da4-b858-4792-acb1-a373a5db9430 Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270 Infante-Varillas, S.F. (Stefany Fiorella)|||/items/e866cf80-70e9-40e9-ad96-f9e8c5179014 Belsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783 Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Sarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160 |
| author |
Llopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20 |
| author_facet |
Llopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20 Aranda-Vega, F. (Fernando)|||/items/967c4675-0318-4d3c-97dc-b5b09026995f Diaz-Valdes, N. (Nancy)|||/items/c3f11da4-b858-4792-acb1-a373a5db9430 Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270 Infante-Varillas, S.F. (Stefany Fiorella)|||/items/e866cf80-70e9-40e9-ad96-f9e8c5179014 Belsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783 Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Sarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160 |
| author_role |
author |
| author2 |
Aranda-Vega, F. (Fernando)|||/items/967c4675-0318-4d3c-97dc-b5b09026995f Diaz-Valdes, N. (Nancy)|||/items/c3f11da4-b858-4792-acb1-a373a5db9430 Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270 Infante-Varillas, S.F. (Stefany Fiorella)|||/items/e866cf80-70e9-40e9-ad96-f9e8c5179014 Belsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783 Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Sarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160 |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Adjuvant Antitumor immunity Blockade Dendritic cells Interleukin-10 Therapeutic vaccination |
| topic |
Adjuvant Antitumor immunity Blockade Dendritic cells Interleukin-10 Therapeutic vaccination |
| description |
Blocking antibodies against immunosuppressive molecules have shown promising results in cancer patients. However, there are not enough data to define those conditions dictating treatment efficacy. In this scenario, IL-10 is a cytokine with controversial effects on tumor growth. Thus, our aim was to characterize in which setting IL-10 blockade may potentiate the beneficial effects of a therapeutic vaccine In the IL-10-expressing B16-OVA and TC-1 P3 (A15) tumor models, therapeutic vaccination with tumor antigens plus the TLR7 ligand Imiquimod increased IL-10 production. Although blockade of IL-10 signal with anti-IL-10R antibodies did not inhibit tumor growth, when combined with vaccination it enhanced tumor rejection, associated with stronger innate and adaptive immune responses. Interestingly, a similar enhancement on immune responses was observed after simultaneous vaccination and IL-10 blockade in naive mice. However, when using vaccines containing as adjuvants the TLR3 ligand poly(I:C) or anti-CD40 agonistic antibodies, despite tumor IL-10 expression, anti-IL-10R antibodies did not provide any beneficial effect on tumor growth and antitumor immune responses. Of note, as opposed to Imiquimod, vaccination with this type of adjuvants did not induce IL-10 and correlated with a lack of in vitro IL-10 production by dendritic cells (DC). Finally, in B16-OVA-bearing mice, blockade of IL-10 during therapeutic vaccination with a multiple adjuvant combination (MAC) with potent immunostimulatory properties but still inducing IL-10 led to superior antitumor immunity and complete tumor rejection. These results suggest that for therapeutic antitumor vaccination, blockade of vaccine-induced IL-10 is more relevant than tumorassociated IL-10. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-01-01 2015 2015-01-01 2024 2024-02-10 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/69048 |
| url |
https://hdl.handle.net/10171/69048 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Taylor & Francis |
| publisher.none.fl_str_mv |
Taylor & Francis |
| dc.source.none.fl_str_mv |
reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
| instname_str |
Universidad de Navarra |
| reponame_str |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
| collection |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
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|
| repository.mail.fl_str_mv |
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1869405695750701056 |
| score |
15,301603 |