Home LiteratureArticle Details
PMID: 16796805 Published · ppublish English Journal Article Review

Role of exosomes in immune regulation.

Journal of cellular and molecular medicine ·Vol. 10 ·No. 2 ·2006-00-00 ·Pages 364-75

Li XB, Zhang ZR, Schluesener HJ, Xu SQ

Abstract

Exosomes are small vesicles originating from late endosomes, 30-100 nm in diameter with typical cup-shape morphology. They are reported to bear high levels of a narrow spectrum of molecules involved in immune response and signal transduction. Apart from removing obsolete membrane proteins, some surprising biological functions of exosomes were unveiled recently and their applications in immunotherapy of tumors are currently intensively investigated. Dendritic cell- (DC) and tumor-derived exosomes have considerable anti-tumor effects in experimental studies and several clinical trials. Despite their potential applications in eliciting a "positive" immune response, exosomes might induce some "unwanted" immune responses, such as immune tolerance and immune evasion. Therefore further investigations about the physiological functions of exosomes and the optimal way of exosome application in tumor immunotherapy are necessary. This review presents recent developments in the field of exosome research and focuses on its applications to tumor immunotherapy.

MeSH Terms
Animals Exocytosis Humans Immunosuppression Therapy/methods Immunotherapy/methods Models, Biological Neoplasms/immunology,therapy Neoplasms, Experimental/immunology,therapy
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Li Xiao-Bo
Institute of Environmental Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Zhang Zhi-Ren
Schluesener Hermann J
Xu Shun-Qing
References (87)
87 references, click to expand
  1. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization.
    Biochem J. 2004 May 15;380(Pt 1):161-71 PMID: 14965343
  2. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth.
    J Exp Med. 1999 Jun 7;189(11):1747-56 PMID: 10359578
  3. MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells.
    Immunol Lett. 2003 Oct 31;89(2-3):125-31 PMID: 14556969
  4. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation.
    J Biol Chem. 2003 Mar 28;278(13):10963-72 PMID: 12519789
  5. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules.
    Blood. 1999 Dec 1;94(11):3791-9 PMID: 10572093
  6. Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes.
    J Immunol. 2001 Jan 15;166(2):868-76 PMID: 11145662
  7. Annexins in membrane traffic.
    Trends Cell Biol. 1993 Jul;3(7):224-7 PMID: 14731757
  8. Vesicles bearing MHC class II molecules mediate transfer of antigen from antigen-presenting cells to CD4+ T cells.
    Eur J Immunol. 1999 Apr;29(4):1363-73 PMID: 10229104
  9. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes.
    Nat Med. 1998 May;4(5):594-600 PMID: 9585234
  10. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.
    J Cell Biol. 1999 Nov 1;147(3):599-610 PMID: 10545503
  11. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes).
    J Biol Chem. 1987 Jul 5;262(19):9412-20 PMID: 3597417
  12. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device.
    J Cell Sci. 2000 Oct;113 Pt 19:3365-74 PMID: 10984428
  13. Direct stimulation of naive T cells by membrane vesicles from antigen-presenting cells: distinct roles for CD54 and B7 molecules.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6670-5 PMID: 12743365
  14. The ins and outs of the transmembrane 4 superfamily.
    Immunol Today. 1994 Dec;15(12):588-94 PMID: 7531445
  15. Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry.
    J Immunol Methods. 2001 Jan 1;247(1-2):163-74 PMID: 11150547
  16. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells.
    Blood. 2004 Nov 15;104(10):3257-66 PMID: 15284116
  17. Association of hepatitis C virus envelope proteins with exosomes.
    Eur J Immunol. 2004 Oct;34(10):2834-42 PMID: 15368299
  18. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes.
    J Cell Biol. 1985 Sep;101(3):942-8 PMID: 2993317
  19. Characteristics of the interaction between Hsc70 and the transferrin receptor in exosomes released during reticulocyte maturation.
    J Biol Chem. 2001 Mar 30;276(13):9910-6 PMID: 11133993
  20. Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccine activity.
    J Immunol. 2001 Jan 1;166(1):490-7 PMID: 11123328
  21. Production and characterization of clinical grade exosomes derived from dendritic cells.
    J Immunol Methods. 2002 Dec 15;270(2):211-26 PMID: 12379326
  22. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells.
    Cancer Res. 2005 Jun 15;65(12):5238-47 PMID: 15958569
  23. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming.
    Nat Med. 2001 Mar;7(3):297-303 PMID: 11231627
  24. Tumor-derived exosomes: a new source of tumor rejection antigens.
    Vaccine. 2002 Dec 19;20 Suppl 4:A28-31 PMID: 12477425
  25. Characterization of Ca2(+)-dependent phospholipid binding, vesicle aggregation and membrane fusion by annexins.
    Biochem J. 1990 Feb 15;266(1):195-200 PMID: 2138016
  26. Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens.
    Methods. 1997 Jun;12(2):165-71 PMID: 9184380
  27. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection.
    Nat Med. 2000 Jul;6(7):769-75 PMID: 10888925
  28. Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection.
    Transplantation. 2003 Nov 27;76(10):1503-10 PMID: 14657694
  29. Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo.
    J Immunol. 2003 Mar 15;170(6):3037-45 PMID: 12626558
  30. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?
    Trends Immunol. 2002 Sep;23(9):445-9 PMID: 12200066
  31. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer.
    J Transl Med. 2005 Feb 21;3(1):9 PMID: 15723705
  32. The immunogenicity of dendritic cell-derived exosomes.
    Blood Cells Mol Dis. 2005 Sep-Oct;35(2):94-110 PMID: 15975838
  33. Annexins: from structure to function.
    Physiol Rev. 2002 Apr;82(2):331-71 PMID: 11917092
  34. Exosomes for cancer immunotherapy.
    Ann Oncol. 2004;15 Suppl 4:iv141-4 PMID: 15477298
  35. The tetraspanin superfamily: molecular facilitators.
    FASEB J. 1997 May;11(6):428-42 PMID: 9194523
  36. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes.
    J Cell Biol. 1983 Aug;97(2):329-39 PMID: 6309857
  37. Exosomes from plasmacytoma cells as a tumor vaccine.
    J Immunother. 2004 Jul-Aug;27(4):282-8 PMID: 15235389
  38. Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects.
    Br J Cancer. 2005 Jan 31;92 (2):305-11 PMID: 15655551
  39. B lymphocytes secrete antigen-presenting vesicles.
    J Exp Med. 1996 Mar 1;183(3):1161-72 PMID: 8642258
  40. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor.
    Cell. 1983 Jul;33(3):967-78 PMID: 6307529
  41. Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial.
    Blood Cells Mol Dis. 2005 Sep-Oct;35(2):149-52 PMID: 16061407
  42. Malignant effusions and immunogenic tumour-derived exosomes.
    Lancet. 2002 Jul 27;360(9329):295-305 PMID: 12147373
  43. Stress-induced proteins in immune response to cancer.
    Curr Top Microbiol Immunol. 1991;167:109-23 PMID: 1711433
  44. The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules.
    J Immunol. 1998 Oct 1;161(7):3282-91 PMID: 9759843
  45. Selective externalization of an ATP-binding protein structurally related to the clathrin-uncoating ATPase/heat shock protein in vesicles containing terminal transferrin receptors during reticulocyte maturation.
    J Biol Chem. 1986 Nov 25;261(33):15368-71 PMID: 3536900
  46. Exosomes: composition, biogenesis and function.
    Nat Rev Immunol. 2002 Aug;2(8):569-79 PMID: 12154376
  47. Phase I trial of intravenous peptide-pulsed dendritic cells in patients with metastatic melanoma.
    J Immunother. 2001 Jan-Feb;24(1):66-78 PMID: 11211150
  48. The potential of exosomes in immunotherapy.
    Expert Opin Biol Ther. 2005 Jun;5(6):737-47 PMID: 15952905
  49. Degradation of AP2 during reticulocyte maturation enhances binding of hsc70 and Alix to a common site on TFR for sorting into exosomes.
    Traffic. 2004 Mar;5(3):181-93 PMID: 15086793
  50. Integrins take partners: cross-talk between integrins and other membrane receptors.
    Trends Cell Biol. 1998 Oct;8(10):390-6 PMID: 9789327
  51. Maturation of function in dendritic cells for tolerance and immunity.
    J Cell Mol Med. 2005 Jul-Sep;9(3):643-54 PMID: 16202211
  52. Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp70.
    J Immunol. 1994 Jun 1;152(11):5398-403 PMID: 8189059
  53. The nature of the subset of MHC class II molecules carrying the CDw78 epitopes.
    Int Immunol. 1999 Apr;11(4):491-8 PMID: 10323201
  54. Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry.
    Proteomics. 2004 Dec;4(12):4019-31 PMID: 15478216
  55. Exosome formation during maturation of mammalian and avian reticulocytes: evidence that exosome release is a major route for externalization of obsolete membrane proteins.
    J Cell Physiol. 1991 Apr;147(1):27-36 PMID: 2037622
  56. Annexin I is phosphorylated in the multivesicular body during the processing of the epidermal growth factor receptor.
    J Cell Biol. 1993 Jan;120(1):77-83 PMID: 8093248
  57. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice.
    Gut. 2003 Dec;52(12):1690-7 PMID: 14633944
  58. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis.
    Blood Cells Mol Dis. 2005 Sep-Oct;35(2):169-73 PMID: 16081306
  59. Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway.
    Traffic. 2003 Apr;4(4):222-31 PMID: 12694561
  60. Protein folding in the cell.
    Nature. 1992 Jan 2;355(6355):33-45 PMID: 1731198
  61. Proteomic analysis of exosomes isolated from human malignant pleural effusions.
    Am J Respir Cell Mol Biol. 2004 Jul;31(1):114-21 PMID: 14975938
  62. Cancer vaccines: finding the best way to train the immune system.
    J Natl Cancer Inst. 2002 Oct 16;94(20):1523-6 PMID: 12381703
  63. Dendritic cell vaccines for cancer immunotherapy.
    Annu Rev Med. 1999;50:507-29 PMID: 10073291
  64. Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo.
    Eur J Immunol. 1994 Mar;24(3):605-10 PMID: 8125131
  65. Dendritic cells: unique leukocyte populations which control the primary immune response.
    Blood. 1997 Nov 1;90(9):3245-87 PMID: 9345009
  66. Exosome-based immunotherapy.
    Cancer Immunol Immunother. 2004 Mar;53(3):234-9 PMID: 14727085
  67. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles.
    J Immunol. 2001 Jun 15;166(12):7309-18 PMID: 11390481
  68. Dendritic cells: a novel therapeutic modality.
    Ann Oncol. 1999 Jan;10(1):21-7 PMID: 10076717
  69. Efficient direct priming of tumor-specific cytotoxic T lymphocyte in vivo by an engineered APC.
    Cancer Res. 1998 Jul 15;58(14):3094-100 PMID: 9679976
  70. Intestinal epithelial cells secrete exosome-like vesicles.
    Gastroenterology. 2001 Aug;121(2):337-49 PMID: 11487543
  71. Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity.
    J Exp Med. 1999 Mar 1;189(5):797-802 PMID: 10049943
  72. Exosomes: endosomal-derived vesicles shipping extracellular messages.
    Curr Opin Cell Biol. 2004 Aug;16(4):415-21 PMID: 15261674
  73. Hsp-70 is closely associated with the transferrin receptor in exosomes from maturing reticulocytes.
    Biochem J. 1995 Jun 15;308 ( Pt 3):823-30 PMID: 8948438
  74. Diacylglycerol kinase alpha regulates the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes.
    J Biol Chem. 2005 Aug 5;280(31):28439-50 PMID: 15870081
  75. More efficient induction of HLA-A*0201-restricted and carcinoembryonic antigen (CEA)-specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells.
    Clin Cancer Res. 2005 Oct 15;11(20):7554-63 PMID: 16243831
  76. The biological role of the Fas/FasL system during tumor formation and progression.
    Semin Cancer Biol. 2002 Aug;12(4):309-15 PMID: 12147205
  77. A common mechanism may be involved in the selective loss of plasma membrane functions during reticulocyte maturation.
    Biomed Biochim Acta. 1990;49(2-3):S70-5 PMID: 2386531
  78. Human small intestinal epithelial cells constitutively express the key elements for antigen processing and the production of exosomes.
    Blood Cells Mol Dis. 2005 Sep-Oct;35(2):122-8 PMID: 16027013
  79. Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes.
    Nat Immunol. 2002 Dec;3(12):1156-62 PMID: 12426563
  80. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial.
    J Transl Med. 2005 Mar 02;3(1):10 PMID: 15740633
  81. Identification of cytoskeleton-associated proteins in isolated rat liver endosomes.
    Biochem J. 1997 Nov 1;327 ( Pt 3):741-6 PMID: 9581551
  82. Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation.
    Mol Biol Cell. 1997 Dec;8(12):2631-45 PMID: 9398681
  83. Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface.
    J Immunol. 2000 Aug 1;165(3):1259-65 PMID: 10903724
  84. Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake.
    J Immunol. 1999 Aug 1;163(3):1398-408 PMID: 10415040
  85. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.
    J Biol Chem. 1998 Aug 7;273(32):20121-7 PMID: 9685355
  86. Molecular chaperones and the immune response.
    Philos Trans R Soc Lond B Biol Sci. 1993 Mar 29;339(1289):363-7; discussion 367-8 PMID: 7684139
  87. Proteomic analysis of exosomes secreted by human mesothelioma cells.
    Am J Pathol. 2004 May;164(5):1807-15 PMID: 15111327
Article Info
Journal
Journal of cellular and molecular medicine
Abbr.
J Cell Mol Med
ISSN
1582-1838
DOI
10.1111/j.1582-4934.2006.tb00405.x
Published
2006-00-00
Pages
364-75
Language
English
Region
England
NLM ID
101083777
PMCID
PMC3933127
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1582-4934.2006.tb00405.x PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2