Title :

Co-delivery of the NKT agonist α-galactosylceramide and tumor antigens to cross-priming dendritic cells breaks tolerance to self-antigens and promotes antitumor responses

Author(s) :

Ghinnagow, Reem [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
de Meester, Julie [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Cruz, Luis Javier [Auteur]
Leiden University Medical Center [LUMC]
Aspord, Caroline [Auteur]
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB]
Corgnac, Stephanie [Auteur]
Immunologie intégrative des tumeurs [UMR 1186]
Macho-Fernandez, Elodie [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Soulard, Daphnée [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Fontaine, Josette [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Chaperot, Laurence [Auteur]
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB]
Charles, Julie [Auteur]
Centre Hospitalier Universitaire [Grenoble] [CHU]
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB]
SONCIN, Fabrice [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Mami-Chouaib, Fathia [Auteur]
Immunologie intégrative des tumeurs [UMR 1186]
Plumas, Joël [Auteur]
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB]
Faveeuw, Christelle [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Trottein, Francois [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Journal title :

Oncoimmunology

Pages :

e1339855

Publisher :

Taylor & Francis

Publication date :

2017-06-08

ISSN :

2162-4011

English keyword(s) :

Cancer
dendritic cells
natural killer T cells
self antigens
targeting
vaccine

HAL domain(s) :

Sciences du Vivant [q-bio]/Immunologie/Vaccinologie

English abstract : [en]

Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8+ T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest ...
Show more >Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8+ T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway. Our results showed for the first time that simultaneous co-delivery of the NKT agonist α-galactosylceramide and tumor self-antigens (Trp2 and gp100) to CD8α+ DCs promotes strong antitumor responses in prophylactic and therapeutic settings (advanced solid tumor model in the mouse). We attributed the vaccine's therapeutic effects to NKT cells (but not to T-helper lymphocytes) and CD8+ T cells. Efficacy was correlated with an elevated ratio between tumor antigen-specific CD8+ T cells and regulatory CD4+ T lymphocytes within the tumor. The nanoparticle-based vaccine actively targeted human CLEC9A-expressing BDCA3+ DCs - the equivalent of murine cross-priming CD8α+ DCs - and induced a strong expansion of effector memory tumor self-antigen (Melan -A)-specific CD8+ T cells from peripheral blood mononuclear cells sourced from healthy donors and melanoma patients. Together, our result shed light on novel therapeutic approaches for controlling tumor development.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL