Les exosomes dérivés des cellules dendritiques

Dendritic cell-derived exosomes

Unité INSERM U520, Institut Curie, 12, rue Lhomond, 75005 Paris, France

Résumé

Les cellules dendritiques (CDs) sont les seules cellules présentatrices d’antigènes capables d’activer les lymphocytes T naïfs, étape indispensable à l’initiation des réponses immunitaires. Nous avons montré que les CDs sécrètent des vésicules membranaires de 60-80 nm de diamètre, appelés exosomes. Les exosomes provoquent de puissantes réponses immunitaires anti-tumorales chez la Souris, et le rejet total et durable de tumeurs établies.

Abstract

Dendritic cells (DC) are potent antigen presenting cells and the only ones capable of inducing primary cytotoxic immune responses both in vivo and vitro. DCs secrete a 60-80 nm membrane vesicle population of endocytic origin, called exosomes. The protein composition of exosomes was analyzed using a systematic proteomic approach. Besides MHC and costimulatory molecules, exosomes bear several adhesion proteins, probably involved in their specific targeting. Exosomes also accumulate several cytosolic factors, most likely involved in exoxome’s biogenesis in late endosomes. Like DCs, exosomes induce potent anti tumor immune responses in vivo. Indeed, a single injection of DC-derived exosomes sensitized with tumor peptides induced the eradication of established mouse tumors. Tumor-specific cytotoxic T lymphocytes were found in the spleen of exosome treated mice, and depletion of CD8⁺ T cells in vivo inhibited the anti tumor effect of exosomes. These results strongly support the implementation of human DC-derived exosomes for cancer immunotherapy.