Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L
Peptide vaccines derived from CD8+ T-cell epitopes have shown variable efficacy in cancer patients. Thus, some peptide vaccines are capable of activating CD8+ T-cell responses, even in the absence of CD4+ T-cell epitopes or dendritic cell (DC)-activating adjuvants. However, the mechanisms underlying...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/69047 |
| Acceso en línea: | https://hdl.handle.net/10171/69047 |
| Access Level: | acceso abierto |
| Palabra clave: | Antitumor vaccines CD8+ T cells CD40L Helper cell-independent Peptide epitopes |
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Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40LLlopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20Huarte, E. (Eduardo)|||/items/c539fbb4-0e58-4af3-8379-6d8422060082Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270Bezunartea, J. (Jaione)|||/items/8f33ef1e-c03e-4e9e-a141-06c02e0f39ddBelsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783Zabaleta-Apiroz, A. (Aintzane)|||/items/b22de5a6-cfd3-41a9-8d6a-004c620cc6a5Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0cPrieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8ccSarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160Antitumor vaccinesCD8+ T cellsCD40LHelper cell-independentPeptide epitopesPeptide vaccines derived from CD8+ T-cell epitopes have shown variable efficacy in cancer patients. Thus, some peptide vaccines are capable of activating CD8+ T-cell responses, even in the absence of CD4+ T-cell epitopes or dendritic cell (DC)-activating adjuvants. However, the mechanisms underlying the clinical activity of these potent peptides are poorly understood. Using CT26 and ovalbumin-expressing B16 murine allograft tumor models, we found that the antitumor effect of helper cell-independent CD8 T-cell peptide vaccines is inhibited by the blockade of CD40 ligand (CD40L) in vivo. Furthermore, in vitro stimulation with antigenic peptides of cells derived from immunized mice induced the expression of CD40L on the surface of CD8+ T cells and fostered DC maturation, an effect that was partially inhibited by CD40L-blocking antibodies. Interestingly, CD40L blockade also inhibited CD8+ T-cell responses, even in the presence of fully mature DCs, suggesting a role for CD40L not only in promoting DC maturation but also in mediating CD8+ T-cell co-stimulation. Importantly, these potent peptides share features with bona fide CD4 epitopes, since they foster responses against less immunogenic CD8+ T-cell epitopes in a CD40L-dependent manner. The analysis of peptides used for the vaccination of cancer patients in clinical trials showed that these peptides also induce the expression of CD40L on the surface of CD8+ T cells. Taken together, these results suggest that CD40L expression induced by potent CD8+ T-cell epitopes can activate antitumor CD8+ T-cell responses, potentially amplifying the immunological responses to less immunogenic CD8+ T-cell epitopes and bypassing the requirement for CD4+ helper T cells in vaccination protocols.Taylor & FrancisDadun. Depósito Académico Digital Universidad de Navarra20242024-02-1020132013-01-0120132013-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/69047reponame: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:10171/690472026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L |
| title |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L |
| spellingShingle |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L Llopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20 Antitumor vaccines CD8+ T cells CD40L Helper cell-independent Peptide epitopes |
| title_short |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L |
| title_full |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L |
| title_fullStr |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L |
| title_full_unstemmed |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L |
| title_sort |
Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L |
| dc.creator.none.fl_str_mv |
Llopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20 Huarte, E. (Eduardo)|||/items/c539fbb4-0e58-4af3-8379-6d8422060082 Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270 Bezunartea, J. (Jaione)|||/items/8f33ef1e-c03e-4e9e-a141-06c02e0f39dd Belsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783 Zabaleta-Apiroz, A. (Aintzane)|||/items/b22de5a6-cfd3-41a9-8d6a-004c620cc6a5 Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc 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 Huarte, E. (Eduardo)|||/items/c539fbb4-0e58-4af3-8379-6d8422060082 Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270 Bezunartea, J. (Jaione)|||/items/8f33ef1e-c03e-4e9e-a141-06c02e0f39dd Belsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783 Zabaleta-Apiroz, A. (Aintzane)|||/items/b22de5a6-cfd3-41a9-8d6a-004c620cc6a5 Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc Sarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160 |
| author_role |
author |
| author2 |
Huarte, E. (Eduardo)|||/items/c539fbb4-0e58-4af3-8379-6d8422060082 Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270 Bezunartea, J. (Jaione)|||/items/8f33ef1e-c03e-4e9e-a141-06c02e0f39dd Belsue, V. (Virginia)|||/items/b372e72d-cb60-4333-bc64-9ada2bb81783 Zabaleta-Apiroz, A. (Aintzane)|||/items/b22de5a6-cfd3-41a9-8d6a-004c620cc6a5 Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc Sarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160 |
| author2_role |
author author 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 |
Antitumor vaccines CD8+ T cells CD40L Helper cell-independent Peptide epitopes |
| topic |
Antitumor vaccines CD8+ T cells CD40L Helper cell-independent Peptide epitopes |
| description |
Peptide vaccines derived from CD8+ T-cell epitopes have shown variable efficacy in cancer patients. Thus, some peptide vaccines are capable of activating CD8+ T-cell responses, even in the absence of CD4+ T-cell epitopes or dendritic cell (DC)-activating adjuvants. However, the mechanisms underlying the clinical activity of these potent peptides are poorly understood. Using CT26 and ovalbumin-expressing B16 murine allograft tumor models, we found that the antitumor effect of helper cell-independent CD8 T-cell peptide vaccines is inhibited by the blockade of CD40 ligand (CD40L) in vivo. Furthermore, in vitro stimulation with antigenic peptides of cells derived from immunized mice induced the expression of CD40L on the surface of CD8+ T cells and fostered DC maturation, an effect that was partially inhibited by CD40L-blocking antibodies. Interestingly, CD40L blockade also inhibited CD8+ T-cell responses, even in the presence of fully mature DCs, suggesting a role for CD40L not only in promoting DC maturation but also in mediating CD8+ T-cell co-stimulation. Importantly, these potent peptides share features with bona fide CD4 epitopes, since they foster responses against less immunogenic CD8+ T-cell epitopes in a CD40L-dependent manner. The analysis of peptides used for the vaccination of cancer patients in clinical trials showed that these peptides also induce the expression of CD40L on the surface of CD8+ T cells. Taken together, these results suggest that CD40L expression induced by potent CD8+ T-cell epitopes can activate antitumor CD8+ T-cell responses, potentially amplifying the immunological responses to less immunogenic CD8+ T-cell epitopes and bypassing the requirement for CD4+ helper T cells in vaccination protocols. |
| publishDate |
2013 |
| dc.date.none.fl_str_mv |
2013 2013-01-01 2013 2013-01-01 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/10171/69047 |
| url |
https://hdl.handle.net/10171/69047 |
| 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 |
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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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1869416610530328576 |
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15,301603 |