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Exosomes for Immunotherapy of Cancer

  • Nathalie Chaput
  • N. E. C. Schartz
  • Fabrice Andre
  • Laurence Zitvogel
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The biology of small vesicles (1–4) secreted from antigen-presenting cells (APCs) recently raised a great deal of interest with the demonstration of their potent immunostimulatory functions in tumor models (5,6). The origin of vesicle secretion was first described (7) in differentiating red blood cells where multivesicular bodies (MVBs) fused with plasma membrane in an exocytic manner. This exocytic pathway was later shown to occur in a wide variety of cell types such as B lymphocytes, mastocytes, immature dendritic cells (DCs), platelets, cytotoxic T lymphocytes (CTLs), fibroblasts, epithelial cells, and tumor cells (6,8–15). Vesicles exocytosed from MVBs into the extracellular medium are referred to as “exosomes” and should not be confused with the more recently described “ribonuclease complex” also named exosome.

Keywords

Major Histocompatibility Complex Major Histocompatibility Complex Class Tumor Rejection Malignant Effusion Immunotherapy Strategy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 2000; 113:3365–3374.PubMedGoogle Scholar
  2. 2.
    Denzer K, van Eijk M, Kleijmeer MJ, Jakobson E, de Groot C, Geuze HJ. Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface. J Immunol 2000; 165:1259–1265.PubMedGoogle Scholar
  3. 3.
    Quah B, O’Neill HC. The application of dendritic cell-derived exosomes in tumour immunotherpy. Cancer Biother Radiopharm 2000; 15:185–194.PubMedCrossRefGoogle Scholar
  4. 4.
    Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, Pomel C, Lhomme C, Escudier B, Le Chevalier T, Tursz T, Amigorena S, Raposo G, Angevin E, Zitvogel L. Malignant effusions and immunogenic tumor derived-exosomes. Lancet 2002; 360:295–305.PubMedCrossRefGoogle Scholar
  5. 5.
    Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cellderived exosomes. Nat Med 1998; 4:594–600.PubMedCrossRefGoogle Scholar
  6. 6.
    Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 2001; 7:297–303.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 1987; 262:9412–9420.PubMedGoogle Scholar
  8. 8.
    Raposo G, Tenza D, Mecheri S, Peronet R, Bonnerot C, Desaymard C. Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation. Mol Biol Cell 1997; 8:2631–2645.PubMedGoogle Scholar
  9. 9.
    Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 1998; 273:20121–20127.PubMedCrossRefGoogle Scholar
  10. 10.
    Arnold PY, Mannie MD. Vesicles bearing MHC class II molecules mediate transfer of antigen-presenting cells to CD4+ cells. Eur J Immunol 1999; 29:1363–1373.PubMedCrossRefGoogle Scholar
  11. 11.
    Heijnen IA, van Vugt MJ, Fanger NA, Graziano RF, de Wit TP, Hofhuis FM, Guyre PM, Capel PJ, Verbeek JS, van de Winkel JG. Antigen targeting to myeloid-specific human Fc gamma RI/CD64 triggers enhanced antibody responses in transgenic mice. J Clin Invest 1996; 97:331–338.PubMedCrossRefGoogle Scholar
  12. 12.
    Hess C, Sadallah S, Hefti A, Landmann R, Schifferli JA. Ectosomes released by human neutrophils are specialized functional units. J Immunol 1999; 163:4564–4573.PubMedGoogle Scholar
  13. 13.
    Patel DM, Arnold PY, White GA, Nardella JP, MD. Mannie Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition. J Immunol 1999; 163:5201–5210.PubMedGoogle Scholar
  14. 14.
    Geminard C, Nault F, Johnstone RM, Vidal M. Characteristics of the interaction between Hsc70 and the transferrin receptor in exosomes released during reticulocyte maturation. J Biol Chem 2001; 276:9910–9916.PubMedCrossRefGoogle Scholar
  15. 15.
    Skokos D, Le Panse S, Villa I, Rousselle JC, Peronet R, David B, Namane A, Mecheri S. Mast celldependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J Immunol 2001; 166:868–876.PubMedGoogle Scholar
  16. 16.
    Lemmon SK, Traub LM. Sorting in the endosomal system in yeast and animal cells. Curr Opin Cell Biol 2000; 12:457–466.PubMedCrossRefGoogle Scholar
  17. 17.
    Odorizzi G, Babst M, Emr SD. Fab 1 p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 1998; 95:847–858.PubMedCrossRefGoogle Scholar
  18. 18.
    Komada M, Soriano P. Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis. Genes Dev 1999; 13:1475–1485.PubMedCrossRefGoogle Scholar
  19. 19.
    Chin LS, Raynor MC, Wei X, Chen HQ, Li L. Hrs interacts with sorting nexin 1 and regulates degradation of epidermal growth factor receptor. J Biol Chem 2001; 276:7069–7078.PubMedCrossRefGoogle Scholar
  20. 20.
    Hemler ME. Specific tetraspanin functions. J Cell Biol 2001; 155:1103–1107.PubMedCrossRefGoogle Scholar
  21. 21.
    Vidal M, Mangeat P, Hoekstra D. Aggregation reroutes molecules from a recycling to a vesicle-mediated secretion pathway during reticulocyte maturation. J Cell Sci 1997; 110:1867–1877.PubMedGoogle Scholar
  22. 22.
    Geminard C, Nault F, Johnstone RM, Vidal M. Characteristics of the interaction between Hsc70 and the transferrin receptor in exosomes released during reticulocyte maturation. J Biol Chem 2001; 276:9910–9916.PubMedCrossRefGoogle Scholar
  23. 23.
    Blanchard N, Lankar D, Faure F, Regnault A, Dumont C, Raposo G, Hivroz C. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/z complex. J Immunol 2002; 168:3235–3242.PubMedGoogle Scholar
  24. 24.
    Peters PJ, Borst J, Oorschot V, Fukuda M, Krahenbuhl O, Tschopp J, Slot JW, Geuze HJ. Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med 1991; 173:1099–1109.PubMedCrossRefGoogle Scholar
  25. 25.
    Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc 73. J Cell Biol 1999; 147:599–610.PubMedCrossRefGoogle Scholar
  26. 26.
    Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, Amigorena S. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 2001; 166:7309–7318.PubMedGoogle Scholar
  27. 27.
    Clayton A, Court J, Navabi H, Adams M, Mason MD, Hobot JA, Newman GR, Jasani B. Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry. J Immunol Methods 2001; 247:163–174.PubMedCrossRefGoogle Scholar
  28. 28.
    Stoorvogel W, Kleijmeer MJ, Geuze HJ, Raposo G. The biogenesis and functions of exosomes. Traffic 2002; 3:321–330.PubMedCrossRefGoogle Scholar
  29. 29.
    Chaput N, Schartz NEC, André F, et al. Exosomes as potent cell free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naïve Tcl lymphocytes leading to tumor rejection. J Immunol. In press.Google Scholar
  30. 30.
    André F, Chaput N, Schartz NEC, et al. Exosomes as potent cell free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class 1/peptide complexes to DC. J Immunol. In press.Google Scholar
  31. 31.
    Thery C, Duban L, Segura E, Veron P, Lantz 0, Amigorena S. Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol 2002; 3:1156–1162.PubMedCrossRefGoogle Scholar
  32. 32.
    Lamparski H, Metha-Damani A, Yao J, Patel S, Hsu D, Ruegg C, Le Pecq J. Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 2002; 270:211.PubMedCrossRefGoogle Scholar
  33. 33.
    Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ. B lymphocytes secrete antigen-presenting vesicles. J Exp Med 1996; 183:1161–1172.PubMedCrossRefGoogle Scholar
  34. 34.
    van Niel G, Raposo G, Candalh C, Boussac M, Hershberg R, Cerf-Bensussan N, Heyman M. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 2001; 121:337–349.PubMedCrossRefGoogle Scholar
  35. 35.
    Angevin E. 7th International Symposium on Dendritic Cells. Abstract 20, p. 28,2002.Google Scholar
  36. 36.
    Pan BT, Teng K, Wu C, Adam M, Johnstone RM. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 1985; 101:942–948.PubMedCrossRefGoogle Scholar
  37. 37.
    Kropshofer H, Spindeldreher S, Rohn TA, Platania N, Grygar C, Daniel N, Wolpl A, Langen H, Horejsi V, Vogt AB. Tetraspan microdomains distinct from lipid rafts enrich select peptide-CMH class II complexes. Nat Immunol 2002; 3:61–68.PubMedCrossRefGoogle Scholar
  38. 38.
    Karlsson M, Lundin S, Dahlgren U, Kahu H, Pettersson I, Telemo E. “Tolerosomes” are produced by intestinal epithelial cells. Eur J Immunol 2001; 31:2892–2900.PubMedCrossRefGoogle Scholar
  39. 39.
    Pêche H. Club Francophone Des Cellules Dendritiques. Abstract C08, p. 31,2001.Google Scholar
  40. 40.
    Huang JF, Yang Y, Sepulveda H, Shi W, Hwang I, Peterson PA, Jackson MR, Sprent J, Cai Z. TCRmediated internalization of peptide-MHC complexes acquired by T cells. Science 1999; 286:952–954.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Nathalie Chaput
  • N. E. C. Schartz
  • Fabrice Andre
  • Laurence Zitvogel

There are no affiliations available

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