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Dendritic Cell-Derived Exosomes Promote Natural Killer Cell Activation and Proliferation: A Role for NKG2D Ligands and IL-15Rα

Authors :
Bernard Escudier
Fabrice Andre
Laurence Zitvogel
Thomas Tursz
Caroline Robert
Sophie Novault
Sophie Viaud
Sophie Caillat-Zucman
Julien Taieb
Nathalie Chaput
Caroline Flament
Magali Terme
Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale
Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Institut Gustave Roussy (IGR)
Hôpital Européen Georges Pompidou [APHP] (HEGP)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561)
Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Hôpital Saint-Vincent de Paul
Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine)
Université Paris-Sud - Paris 11 (UP11)
QLRT-2001-00093, AP-HP, ARC Institut Gustave Roussy, the Young Investigator Award, ASCO 2002, the EC Cell factory program project, ALLOSTEM European grant, the Ligue labellisée contre le cancer and Cancéropçle Ile de France.
Novault, Sophie
Source :
PLoS ONE, PLoS ONE, Public Library of Science, 2009, 4 (3), pp.e4942. ⟨10.1371/journal.pone.0004942⟩, PLoS ONE, Vol 4, Iss 3, p e4942 (2009), PLoS ONE, 2009, 4 (3), pp.e4942. ⟨10.1371/journal.pone.0004942⟩
Publication Year :
2009
Publisher :
HAL CCSD, 2009.

Abstract

International audience; Dendritic cell (DC) derived-exosomes (Dex) are nanomeric vesicles harboring functional MHC/peptide complexes promoting T cell-dependent tumor rejection. In the first Phase I trial using peptide-pulsed Dex, the observation of clinical regressions in the absence of T cell responses prompted the search for alternate effector mechanisms. Mouse studies unraveled the bioactivity of Dex on NK cells. Indeed, Dex promoted an IL-15Ralpha- and NKG2D-dependent NK cell proliferation and activation respectively, resulting in anti-metastatic effects mediated by NK1.1(+) cells. In humans, Dex express functional IL-15Ralpha which allow proliferation and IFNgamma secretion by NK cells. In contrast to immature DC, human Dex harbor NKG2D ligands on their surface leading to a direct engagement of NKG2D and NK cell activation ex vivo. In our phase I clinical trial, we highlight the capacity of Dex based-vaccines to restore the number and NKG2D-dependent function of NK cells in 7/14 patients. Altogether, these data provide a mechanistic explanation on how Dex may stimulate non MHC restricted-anti-tumor effectors and induce tumor regression in vivo.

Details

Language :
English
ISSN :
19326203
Database :
OpenAIRE
Journal :
PLoS ONE, PLoS ONE, Public Library of Science, 2009, 4 (3), pp.e4942. ⟨10.1371/journal.pone.0004942⟩, PLoS ONE, Vol 4, Iss 3, p e4942 (2009), PLoS ONE, 2009, 4 (3), pp.e4942. ⟨10.1371/journal.pone.0004942⟩
Accession number :
edsair.doi.dedup.....ab6730bf7ddc9ddf64c3b2aa004c8e0f