Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12
OBJECTIVE: Injection of dendritic cells (DC) engineered with recombinant adenoviral vectors to produce interleukin-12 (IL-12) inside experimental murine tumors frequently achieves complete regressions. In such a system the function of CD8(+) T cells has been shown to be an absolute requirement, in c...
| Autores: | , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2002 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/21789 |
| Acesso em linha: | https://hdl.handle.net/10171/21789 |
| Access Level: | acceso abierto |
| Palavra-chave: | Dendritic Cells/immunology Dendritic Cells/transplantation Genetic Engineering Immunotherapy Interleukin-12/genetics Killer Cells, Natural/immunology Neoplasms, Experimental/therapy |
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oai:dadun.unav.edu:10171/21789 |
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España |
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Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12Rodriguez-Calvillo, M. (Mercedes)|||/items/41d9968c-53d4-4a20-9407-f47eb3d91986Duarte, M. (Marina)|||/items/337bbd63-de77-4f64-8a06-cfcf2f579f77Tirapu, I. (Íñigo)|||/items/c563bf91-df49-4b18-b715-76b1b014d0e0Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91Mazzolini, G. (Guillermo)|||/items/73a250e4-d50b-45d7-bf6b-f222192f702eQian, C. (Cheng)|||/items/49f586b0-dcc7-4e30-82f4-91f3c38ecc37Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4eDendritic Cells/immunologyDendritic Cells/transplantationGenetic EngineeringImmunotherapyInterleukin-12/geneticsKiller Cells, Natural/immunologyNeoplasms, Experimental/therapyOBJECTIVE: Injection of dendritic cells (DC) engineered with recombinant adenoviral vectors to produce interleukin-12 (IL-12) inside experimental murine tumors frequently achieves complete regressions. In such a system the function of CD8(+) T cells has been shown to be an absolute requirement, in contrast to observations made upon depletion of CD4(+) T cells, which minimally affected the outcome. The aim of this work was to study the possible involvement of natural killer (NK) cells in this setting. MATERIALS, METHODS, AND RESULTS: Depletions with anti-AsialoGM1 antiserum showed only a small decrease in the proportion of complete regressions obtained that correlated with induction of NK activities in lymphatic tissues into which DC migrate, whereas combined depletions of CD4(+) and NK cells completely eliminated the antitumor effects. Likewise in vivo neutralization of interferon-gamma (IFN-gamma) also eliminated those therapeutic effects. Trying to define the cellular role played by NK cells in vivo, it was observed that injection of cultured DC inside the spleen of T- and B-cell-deficient (Rag1(-/-)) mice induced upregulation of NK activity only if DC had been adenovirally engineered to produce IL-12. In addition, identically transfected fibroblasts also activated NK cells, indicating that IL-12 transfection was the unique requirement. Equivalent human DC only activated in vitro the cytolytic and cytokine-secreting functions of autologous NK cells if transfected to express human IL-12. CONCLUSIONS: Overall, these results point out an important role played by NK cell activation in the potent immunotherapeutic effects elicited by intratumoral injection of IL-12--secreting DC and that NK activation under these conditions is mainly, if not only, dependent on IL-12.ElsevierDadun. Depósito Académico Digital Universidad de Navarra20122012-04-2520022002-01-0120022002-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/21789reponame: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:10171/217892026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 |
| title |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 |
| spellingShingle |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 Rodriguez-Calvillo, M. (Mercedes)|||/items/41d9968c-53d4-4a20-9407-f47eb3d91986 Dendritic Cells/immunology Dendritic Cells/transplantation Genetic Engineering Immunotherapy Interleukin-12/genetics Killer Cells, Natural/immunology Neoplasms, Experimental/therapy |
| title_short |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 |
| title_full |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 |
| title_fullStr |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 |
| title_full_unstemmed |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 |
| title_sort |
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12 |
| dc.creator.none.fl_str_mv |
Rodriguez-Calvillo, M. (Mercedes)|||/items/41d9968c-53d4-4a20-9407-f47eb3d91986 Duarte, M. (Marina)|||/items/337bbd63-de77-4f64-8a06-cfcf2f579f77 Tirapu, I. (Íñigo)|||/items/c563bf91-df49-4b18-b715-76b1b014d0e0 Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91 Mazzolini, G. (Guillermo)|||/items/73a250e4-d50b-45d7-bf6b-f222192f702e Qian, C. (Cheng)|||/items/49f586b0-dcc7-4e30-82f4-91f3c38ecc37 Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e |
| author |
Rodriguez-Calvillo, M. (Mercedes)|||/items/41d9968c-53d4-4a20-9407-f47eb3d91986 |
| author_facet |
Rodriguez-Calvillo, M. (Mercedes)|||/items/41d9968c-53d4-4a20-9407-f47eb3d91986 Duarte, M. (Marina)|||/items/337bbd63-de77-4f64-8a06-cfcf2f579f77 Tirapu, I. (Íñigo)|||/items/c563bf91-df49-4b18-b715-76b1b014d0e0 Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91 Mazzolini, G. (Guillermo)|||/items/73a250e4-d50b-45d7-bf6b-f222192f702e Qian, C. (Cheng)|||/items/49f586b0-dcc7-4e30-82f4-91f3c38ecc37 Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e |
| author_role |
author |
| author2 |
Duarte, M. (Marina)|||/items/337bbd63-de77-4f64-8a06-cfcf2f579f77 Tirapu, I. (Íñigo)|||/items/c563bf91-df49-4b18-b715-76b1b014d0e0 Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91 Mazzolini, G. (Guillermo)|||/items/73a250e4-d50b-45d7-bf6b-f222192f702e Qian, C. (Cheng)|||/items/49f586b0-dcc7-4e30-82f4-91f3c38ecc37 Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e |
| 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 |
Dendritic Cells/immunology Dendritic Cells/transplantation Genetic Engineering Immunotherapy Interleukin-12/genetics Killer Cells, Natural/immunology Neoplasms, Experimental/therapy |
| topic |
Dendritic Cells/immunology Dendritic Cells/transplantation Genetic Engineering Immunotherapy Interleukin-12/genetics Killer Cells, Natural/immunology Neoplasms, Experimental/therapy |
| description |
OBJECTIVE: Injection of dendritic cells (DC) engineered with recombinant adenoviral vectors to produce interleukin-12 (IL-12) inside experimental murine tumors frequently achieves complete regressions. In such a system the function of CD8(+) T cells has been shown to be an absolute requirement, in contrast to observations made upon depletion of CD4(+) T cells, which minimally affected the outcome. The aim of this work was to study the possible involvement of natural killer (NK) cells in this setting. MATERIALS, METHODS, AND RESULTS: Depletions with anti-AsialoGM1 antiserum showed only a small decrease in the proportion of complete regressions obtained that correlated with induction of NK activities in lymphatic tissues into which DC migrate, whereas combined depletions of CD4(+) and NK cells completely eliminated the antitumor effects. Likewise in vivo neutralization of interferon-gamma (IFN-gamma) also eliminated those therapeutic effects. Trying to define the cellular role played by NK cells in vivo, it was observed that injection of cultured DC inside the spleen of T- and B-cell-deficient (Rag1(-/-)) mice induced upregulation of NK activity only if DC had been adenovirally engineered to produce IL-12. In addition, identically transfected fibroblasts also activated NK cells, indicating that IL-12 transfection was the unique requirement. Equivalent human DC only activated in vitro the cytolytic and cytokine-secreting functions of autologous NK cells if transfected to express human IL-12. CONCLUSIONS: Overall, these results point out an important role played by NK cell activation in the potent immunotherapeutic effects elicited by intratumoral injection of IL-12--secreting DC and that NK activation under these conditions is mainly, if not only, dependent on IL-12. |
| publishDate |
2002 |
| dc.date.none.fl_str_mv |
2002 2002-01-01 2002 2002-01-01 2012 2012-04-25 |
| 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/10171/21789 |
| url |
https://hdl.handle.net/10171/21789 |
| 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 |
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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 |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
| instname_str |
Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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| repository.mail.fl_str_mv |
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1869423621295833088 |
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15,300719 |