The emerging roles of exosomes in leukemogeneis

Oncotarget

Volumn 7, Issue 31, 2016, Pages 50698-50707

  Zhou, Jianbiao ^a,b   Wang, Sam ^c   Sun, Kangyun ^d   Chng, Wee Joo ^a,b,e  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b Dept Medicine Endocrinol Diabet   (Singapore)

^c UNIVERSITY OF TORONTO   (Canada)

^d NANJING MEDICAL UNIVERSITY   (China)

^e NATIONAL UNIVERSITY HEALTH SYSTEM   (Singapore)

Author keywords

Biomarker; Exosome; Immunotherapy; Leukemia; miRNA

Indexed keywords

BIOLOGICAL MARKER; GALECTIN 3; MICRORNA 126; SOMATOMEDIN C RECEPTOR; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; ANTINEOPLASTIC AGENT; PROTEIN; RNA;

ACUTE MYELOBLASTIC LEUKEMIA; APOPTOSIS; BIOGENESIS; BONE MARROW BIOPSY; BONE MARROW STROMA CELL; CANCER CHEMOTHERAPY; CANCER DIAGNOSIS; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; CANCER RESISTANCE; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; DENDRITIC CELL; DRUG DELIVERY SYSTEM; EXOSOME; FLOW CYTOMETRY; GRAFT VERSUS HOST REACTION; HUMAN; IMMUNE RESPONSE; IN VIVO STUDY; LEUKEMIA; LEUKEMIA CELL; LEUKEMOGENESIS; MESENCHYMAL STEM CELL; NONHUMAN; REVIEW; TUMOR ESCAPE; TUMOR MICROENVIRONMENT; TUMOR VASCULARIZATION; ANIMAL; CELL COMMUNICATION; CELL MOTION; DRUG RESISTANCE; ENDOSOME; GENE EXPRESSION REGULATION; IMMUNOTHERAPY; METABOLISM; MOUSE; NEOVASCULARIZATION (PATHOLOGY); PROGNOSIS; TREATMENT OUTCOME;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL COMMUNICATION; CELL MOVEMENT; CELL PROLIFERATION; CELL SURVIVAL; DRUG RESISTANCE, NEOPLASM; ENDOSOMES; EXOSOMES; GENE EXPRESSION REGULATION, LEUKEMIC; HUMANS; IMMUNOTHERAPY; LEUKEMIA; MICE; NEOVASCULARIZATION, PATHOLOGIC; PROGNOSIS; PROTEINS; RNA; TREATMENT OUTCOME;

EID: 84981311903     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9333     Document Type: Review

References (85)

1. Keller S, Sanderson MP, Stoeck A and Altevogt P. Exosomes: from biogenesis and secretion to biological function. Immunology letters. 2006; 107:102-108.
2. Johnstone RM, Adam M, Hammond JR, Orr L and Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). The Journal of biological chemistry. 1987; 262:9412-9420.
3. Mathivanan S, Ji H and Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. Journal of proteomics. 2010; 73:1907-1920.
4. van der Pol E, Boing AN, Harrison P, Sturk A and Nieuwland R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacological reviews. 2012; 64:676-705.
5. Kowal J, Tkach M and Thery C. Biogenesis and secretion of exosomes. Current opinion in cell biology. 2014; 29:116-125.
6. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brugger B and Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008; 319:1244-1247.
7. Cocucci E and Meldolesi J. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 2015; 25:364-372.
8. Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J and Amigorena S. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. Journal of immunology. 2001; 166:7309-7318.
9. Xiao D, Ohlendorf J, Chen Y, Taylor DD, Rai SN, Waigel S, Zacharias W, Hao H and McMasters KM. Identifying mRNA, microRNA and protein profiles of melanoma exosomes. PLoS One. 2012; 7:e46874.
10. Keerthikumar S, Chisanga D, Ariyaratne D, Al Saffar H, Anand S, Zhao K, Samuel M, Pathan M, Jois M, Chilamkurti N, Gangoda L and Mathivanan S. ExoCarta: A Web-Based Compendium of Exosomal Cargo. Journal of molecular biology. 2015.
11. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ and Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature cell biology. 2007; 9:654-659.
12. Record M, Subra C, Silvente-Poirot S and Poirot M. Exosomes as intercellular signalosomes and pharmacological effectors. Biochemical pharmacology. 2011; 81:1171-1182.
13. Luga V and Wrana JL. Tumor-stroma interaction: Revealing fibroblast-secreted exosomes as potent regulators of Wntplanar cell polarity signaling in cancer metastasis. Cancer research. 2013; 73:6843-6847.
14. Suetsugu A, Honma K, Saji S, Moriwaki H, Ochiya T and Hoffman RM. Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models. Advanced drug delivery reviews. 2013; 65:383-390.
15. Kumar B, Garcia M, Murakami JL and Chen CC. Exosomemediated microenvironment dysregulation in leukemia. Biochimica et biophysica acta. 2016; 1863:464-470.
16. Katsuda T, Kosaka N and Ochiya T. The roles of extracellular vesicles in cancer biology: toward the development of novel cancer biomarkers. Proteomics. 2014; 14:412-425.
17. Raimondo S, Corrado C, Raimondi L, De Leo G and Alessandro R. Role of Extracellular Vesicles in Hematological Malignancies. BioMed research international. 2015; 2015:821613.
18. Vinay DS, Ryan EP, Pawelec G, Talib WH, Stagg J, Elkord E, Lichtor T, Decker WK, Whelan RL, Kumara HM, Signori E, Honoki K, Georgakilas AG, Amin A, Helferich WG, Boosani CS, et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Seminars in cancer biology. 2015; 35 Suppl:S185-198.
19. Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM and Karlsson S. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proceedings of the National Academy of Sciences of the United States of America. 1993; 90:770-774.
20. Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB and Fauci AS. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. The Journal of experimental medicine. 1986; 163:1037-1050.
21. Szczepanski MJ, Szajnik M, Welsh A, Whiteside TL and Boyiadzis M. Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1. Haematologica. 2011; 96:1302-1309.
22. Hong CS, Muller L, Whiteside TL and Boyiadzis M. Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia. Frontiers in immunology. 2014; 5:160.
23. Webber JP, Spary LK, Sanders AJ, Chowdhury R, Jiang WG, Steadman R, Wymant J, Jones AT, Kynaston H, Mason MD, Tabi Z and Clayton A. Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene. 2015; 34:290-302.
24. Webber J, Steadman R, Mason MD, Tabi Z and Clayton A. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer research. 2010; 70:9621-9630.
25. Wada J, Onishi H, Suzuki H, Yamasaki A, Nagai S, Morisaki T and Katano M. Surface-bound TGF-beta1 on effusion-derived exosomes participates in maintenance of number and suppressive function of regulatory T-cells in malignant effusions. Anticancer research. 2010; 30:3747-3757.
26. Xie Y, Bai O, Yuan J, Chibbar R, Slattery K, Wei Y, Deng Y and Xiang J. Tumor apoptotic bodies inhibit CTL responses and antitumor immunity via membrane-bound transforming growth factor-beta1 inducing CD8+ T-cell anergy and CD4+ Tr1 cell responses. Cancer research. 2009; 69:7756-7766.
27. Clayton A, Mitchell JP, Court J, Linnane S, Mason MD and Tabi Z. Human tumor-derived exosomes down-modulate NKG2D expression. Journal of immunology. 2008; 180:7249-7258.
28. Clayton A, Mitchell JP, Court J, Mason MD and Tabi Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer research. 2007; 67:7458-7466.
29. Huan J, Hornick NI, Shurtleff MJ, Skinner AM, Goloviznina NA, Roberts CT, Jr. and Kurre P. RNA trafficking by acute myelogenous leukemia exosomes. Cancer research. 2013; 73:918-929.
30. Taverna S, Amodeo V, Saieva L, Russo A, Giallombardo M, De Leo G and Alessandro R. Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells. Molecular cancer. 2014; 13:169.
31. Corrado C, Raimondo S, Saieva L, Flugy AM, De Leo G and Alessandro R. Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells. Cancer letters. 2014; 348:71-76.
32. Zhou J, Ching YQ and Chng WJ. Aberrant nuclear factorkappa B activity in acute myeloid leukemia: from molecular pathogenesis to therapeutic target. Oncotarget. 2015; 6:5490-5500. doi: 10.18632/oncotarget.3545.
33. Zhou J, Cheong LL, Liu SC, Chong PS, Mahara S, Bi C, Ong KO, Zeng Q and Chng WJ. The pro-metastasis tyrosine phosphatase, PRL-3 (PTP4A3), is a novel mediator of oncogenic function of BCR-ABL in human chronic myeloid leukemia. Molecular cancer. 2012; 11:72.
34. Raimondo S, Saieva L, Corrado C, Fontana S, Flugy A, Rizzo A, De Leo G and Alessandro R. Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. CCS. 2015; 13:8.
35. Jaworski E, Narayanan A, Van Duyne R, Shabbeer-Meyering S, Iordanskiy S, Saifuddin M, Das R, Afonso PV, Sampey GC, Chung M, Popratiloff A, Shrestha B, Sehgal M, Jain P, Vertes A, Mahieux R, et al. Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein. The Journal of biological chemistry. 2014; 289:22284-22305.
36. Zhou J, Mauerer K, Farina L and Gribben JG. The role of the tumor microenvironment in hematological malignancies and implication for therapy. Frontiers in bioscience. 2005; 10:1581-1596.
37. Isidori A, Salvestrini V, Ciciarello M, Loscocco F, Visani G, Parisi S, Lecciso M, Ocadlikova D, Rossi L, Gabucci E, Clissa C and Curti A. The role of the immunosuppressive microenvironment in acute myeloid leukemia development and treatment. Expert review of hematology. 2014; 7:807-818.
38. Mineo M, Garfield SH, Taverna S, Flugy A, De Leo G, Alessandro R and Kohn EC. Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a Src-dependent fashion. Angiogenesis. 2012; 15:33-45.
39. Umezu T, Ohyashiki K, Kuroda M and Ohyashiki JH. Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene. 2013; 32:2747-2755.
40. Li S. Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia. Leukemia & lymphoma. 2008; 49:19-26.
41. Kuehbacher A, Urbich C and Dimmeler S. Targeting microRNA expression to regulate angiogenesis. Trends in pharmacological sciences. 2008; 29:12-15.
42. Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Y, Urbich C, Hofmann WK, Zeiher AM and Dimmeler S. Members of the microRNA-17-92 cluster exhibit a cellintrinsic antiangiogenic function in endothelial cells. Blood. 2010; 115:4944-4950.
43. Tadokoro H, Umezu T, Ohyashiki K, Hirano T and Ohyashiki JH. Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. The Journal of biological chemistry. 2013; 288:34343-34351.
44. Taverna S, Flugy A, Saieva L, Kohn EC, Santoro A, Meraviglia S, De Leo G and Alessandro R. Role of exosomes released by chronic myelogenous leukemia cells in angiogenesis. International journal of cancer. 2012; 130:2033-2043.
45. Fang Y, Garnier D, Lee TH, D'Asti E, Montermini L, Meehan B and Rak J. PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells. Angiogenesis. 2016; 19:25-38.
46. Manabe A, Coustan-Smith E, Behm FG, Raimondi SC and Campana D. Bone marrow-derived stromal cells prevent apoptotic cell death in B-lineage acute lymphoblastic leukemia. Blood. 1992; 79:2370-2377.
47. Bendall LJ, Daniel A, Kortlepel K and Gottlieb DJ. Bone marrow adherent layers inhibit apoptosis of acute myeloid leukemia cells. Experimental hematology. 1994; 22:1252-1260.
48. Panayiotidis P, Jones D, Ganeshaguru K, Foroni L and Hoffbrand AV. Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. British journal of haematology. 1996; 92:97-103.
49. Konopleva M, Konoplev S, Hu W, Zaritskey AY, Afanasiev BV and Andreeff M. Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia. 2002; 16:1713-1724.
50. Viola S, Traer E, Huan J, Hornick NI, Tyner JW, Agarwal A, Loriaux M, Johnstone B and Kurre P. Alterations in acute myeloid leukaemia bone marrow stromal cell exosome content coincide with gains in tyrosine kinase inhibitor resistance. British journal of haematology. 2015.
51. Pena C, Mirandola L, Figueroa JA, Hosiriluck N, Suvorava N, Trotter K, Reidy A, Rakhshanda R, Payne D, Jenkins M, Grizzi F, Littlefield L, Chiriva-Internati M and Cobos E. Galectins as therapeutic targets for hematological malignancies: a hopeful sweetness. Annals of translational medicine. 2014; 2:87.
52. Giordano M, Croci DO and Rabinovich GA. Galectins in hematological malignancies. Current opinion in hematology. 2013; 20:327-335.
53. Fortuna-Costa A, Gomes AM, Kozlowski EO, Stelling MP and Pavao MS. Extracellular galectin-3 in tumor progression and metastasis. Frontiers in oncology. 2014; 4:138.
54. Thijssen VL, Heusschen R, Caers J and Griffioen AW. Galectin expression in cancer diagnosis and prognosis: A systematic review. Biochimica et biophysica acta. 2015; 1855:235-247.
55. Funasaka T, Raz A and Nangia-Makker P. Galectin-3 in angiogenesis and metastasis. Glycobiology. 2014; 24:886-891.
56. Cheng YL, Huang WC, Chen CL, Tsai CC, Wang CY, Chiu WH, Chen YL, Lin YS, Chang CF and Lin CF. Increased galectin-3 facilitates leukemia cell survival from apoptotic stimuli. Biochemical and biophysical research communications. 2011; 412:334-340.
57. Hu K, Gu Y, Lou L, Liu L, Hu Y, Wang B, Luo Y, Shi J, Yu X and Huang H. Galectin-3 mediates bone marrow microenvironment-induced drug resistance in acute leukemia cells via Wnt/beta-catenin signaling pathway. J Hematol Oncol. 2015; 8:1.
58. Yamamoto-Sugitani M, Kuroda J, Ashihara E, Nagoshi H, Kobayashi T, Matsumoto Y, Sasaki N, Shimura Y, Kiyota M, Nakayama R, Akaji K, Taki T, Uoshima N, Kobayashi Y, Horiike S, Maekawa T, et al. Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108:17468-17473.
59. Cheng CL, Hou HA, Lee MC, Liu CY, Jhuang JY, Lai YJ, Lin CW, Chen HY, Liu FT, Chou WC, Chen CY, Tang JL, Yao M, Huang SY, Ko BS, Wu SJ, et al. Higher bone marrow LGALS3 expression is an independent unfavorable prognostic factor for overall survival in patients with acute myeloid leukemia. Blood. 2013; 121:3172-3180.
60. Fei F, Joo EJ, Tarighat SS, Schiffer I, Paz H, Fabbri M, Abdel-Azim H, Groffen J and Heisterkamp N. B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3. Oncotarget. 2015; 6:11378-11394. doi: 10.18632/oncotarget.3409.
61. Hornick NI, Huan J, Doron B, Goloviznina NA, Lapidus J, Chang BH and Kurre P. Serum Exosome MicroRNA as a Minimally-Invasive Early Biomarker of AML. Scientific reports. 2015; 5:11295.
62. Li M, Zeringer E, Barta T, Schageman J, Cheng A and Vlassov AV. Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 2014; 369.
63. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, Piwnica-Worms D and Kalluri R. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015; 523:177-182.
64. Caivano A, Laurenzana I, De Luca L, La Rocca F, Simeon V, Trino S, D'Auria F, Traficante A, Maietti M, Izzo T, D'Arena G, Mansueto G, Pietrantuono G, Laurenti L, Musto P and Del Vecchio L. High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders. Tumour biology. 2015; 36:9739-9752.
65. Morelli AE, Larregina AT, Shufesky WJ, Sullivan ML, Stolz DB, Papworth GD, Zahorchak AF, Logar AJ, Wang Z, Watkins SC, Falo LD, Jr. and Thomson AW. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood. 2004; 104:3257-3266.
66. Wahlgren J, De LKT, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P and Valadi H. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic acids research. 2012; 40:e130.
67. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Wurdinger T and Middeldorp JM. Functional delivery of viral miRNAs via exosomes. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107:6328-6333.
68. Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, Boireau W, Rouleau A, Simon B, Lanneau D, De Thonel A, Multhoff G, Hamman A, Martin F, Chauffert B, Solary E, et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. The Journal of clinical investigation. 2010; 120:457-471.
69. Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, Marra M, Lugini L, Logozzi M, Lozupone F, Federici C, Iessi E, Parmiani G, Arancia G, Belardelli F and Fais S. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. Journal of the National Cancer Institute. 2004; 96:1702-1713.
70. Koch R, Aung T, Vogel D, Chapuy B, Wenzel D, Becker S, Sinzig U, Venkataramani V, von Mach T, Jacob R, Truemper L and Wulf GG. Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone. Clinical cancer research. 2016; 22:395-404.
71. Marleau AM, Chen CS, Joyce JA and Tullis RH. Exosome removal as a therapeutic adjuvant in cancer. Journal of translational medicine. 2012; 10:134.
72. Hanke N, Alizadeh D, Katsanis E and Larmonier N. Dendritic cell tumor killing activity and its potential applications in cancer immunotherapy. Critical reviews in immunology. 2013; 33:1-21.
73. Guo F, Chang CK, Fan HH, Nie XX, Ren YN, Liu YY and Zhao LH. Anti-tumour effects of exosomes in combination with cyclophosphamide and polyinosinic-polycytidylic acid. The Journal of international medical research. 2008; 36:1342-1353.
74. Gu X, Erb U, Buchler MW and Zoller M. Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice. International journal of cancer. 2015; 136:E74-84.
75. Shen C, Hao SG, Zhao CX, Zhu J and Wang C. Antileukaemia immunity: effect of exosomes against NB4 acute promyelocytic leukaemia cells. The Journal of international medical research. 2011; 39:740-747.
76. Bu N, Li QL, Feng Q and Sun BZ. Immune protection effect of exosomes against attack of L1210 tumor cells. Leukemia & lymphoma. 2006; 47:913-918.
77. Ruiss R, Jochum S, Mocikat R, Hammerschmidt W and Zeidler R. EBV-gp350 confers B-cell tropism to tailored exosomes and is a neo-antigen in normal and malignant B cells-a new option for the treatment of B-CLL. PLoS One. 2011; 6:e25294.
78. Romagnoli GG, Zelante BB, Toniolo PA, Migliori IK and Barbuto JA. Dendritic Cell-Derived Exosomes may be a Tool for Cancer Immunotherapy by Converting Tumor Cells into Immunogenic Targets. Frontiers in immunology. 2014; 5:692.
79. Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M and Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004; 363:1439-1441.
80. Yeo RW, Lai RC, Zhang B, Tan SS, Yin Y, Teh BJ and Lim SK. Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Advanced drug delivery reviews. 2013; 65:336-341.
81. Tominaga N, Yoshioka Y and Ochiya T. A novel platform for cancer therapy using extracellular vesicles. Advanced drug delivery reviews. 2015; 95:50-55.
82. Akao Y, Iio A, Itoh T, Noguchi S, Itoh Y, Ohtsuki Y and Naoe T. Microvesicle-mediated RNA molecule delivery system using monocytes/macrophages. Molecular therapy. 2011; 19:395-399.
83. Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, Boccaccio C, Bonnerot C, Dhellin O, Movassagh M, Piperno S, Robert C, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. Journal of translational medicine. 2005; 3:10.
84. Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, Valente N, Shreeniwas R, Sutton MA, Delcayre A, Hsu DH, Le Pecq JB and Lyerly HK. A phase I study of dexosome immunotherapy in patients with advanced nonsmall cell lung cancer. Journal of translational medicine. 2005; 3:9.
85. Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H and Li G. Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Molecular therapy. 2008; 16:782-790.