Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming

Abstract

The initiation of T-cell–mediated antitumor immune responses requires the uptake and processing of tumor antigens by dendritic cells and their presentation on MHC-I molecules. Here we show in a human in vitro model system that exosomes, a population of small membrane vesicles secreted by living tumor cells, contain and transfer tumor antigens to dendritic cells. After mouse tumor exosome uptake, dendritic cells induce potent CD8+ T-cell–dependent antitumor effects on syngeneic and allogeneic established mouse tumors. Therefore, exosomes represent a novel source of tumor-rejection antigens for T-cell cross priming, relevant for immunointerventions.

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Figure 1: Tumor cells display multivesicular bodies and secrete exosomes.
Figure 2: Cross-immunizations using tumor-derived exosomes.
Figure 3: Dendritic cells loaded with exosomes promote cross-protective antitumor effects.
Figure 4: Exosomes mediate CD4+ and CD8+ T-cell–dependent antitumor effects.
Figure 5: Melanoma-derived exosomes transfer tumor antigens to MD-DCs.
Figure 6: Tumor-derived exosomes contain HSP70 and whole native tumor antigens.

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Acknowledgements

We thank F. André, A. Caignard and C. Bonnerot for helpful discussions; M.-F. Avril for providing us with melanoma patient-derived tumor material; A. Le Cesne for blood samples; S. Koscielny for statistical analysis; and the staff of the animal facility for animal care and handling. This work was supported by the Ligue Française de Lutte Contre le Cancer 'Axe Immunologie des Tumeurs', INSERM, CNRS, APCells SA and Inc., GEFLUC and Association pour la Recherche Contre Le Cancer ARC. J.W. was supported by Ligue Nationale de Lutte Contre le Cancer, A.L. by ARC.

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Correspondence to Sebastian Amigorena or Laurence Zitvogel.

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Wolfers, J., Lozier, A., Raposo, G. et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7, 297–303 (2001). https://doi.org/10.1038/85438

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