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- Title
Dendritic Cell-Derived Exosomes Promote Natural Killer Cell Activation and Proliferation: A Role for NKG2D Ligands and IL-15Rα.
- Authors
Viaud, Sophie; Terme, Magali; Flament, Caroline; Taieb, Julien; André, Fabrice; Novault, Sophie; Escudier, Bernard; Robert, Caroline; Caillat-Zucman, Sophie; Tursz, Thomas; Zitvogel, Laurence; Chaput, Nathalie
- Abstract
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-15Ra- 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-15Rα which allow proliferation and IFNγ 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.
- Subjects
DENDRITIC cells; KILLER cells; T cells; LIGANDS (Biochemistry); SYNAPTIC vesicles; REGRESSION analysis; METASTASIS; DISEASE remission
- Publication
PLoS ONE, 2009, Vol 4, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0004942