1932

Abstract

Exosomes are small, single-membrane, secreted organelles of ∼30 to ∼200 nm in diameter that have the same topology as the cell and are enriched in selected proteins, lipids, nucleic acids, and glycoconjugates. Exosomes contain an array of membrane-associated, high-order oligomeric protein complexes, display pronounced molecular heterogeneity, and are created by budding at both plasma and endosome membranes. Exosome biogenesis is a mechanism of protein quality control, and once released, exosomes have activities as diverse as remodeling the extracellular matrix and transmitting signals and molecules to other cells. This pathway of intercellular vesicle traffic plays important roles in many aspects of human health and disease, including development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases. In addition, viruses co-opt exosome biogenesis pathways both for assembling infectious particles and for establishing host permissiveness. On the basis of these and other properties, exosomes are being developed as therapeutic agents in multiple disease models.

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2019-06-20
2024-06-25
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Literature Cited

  1. 1. 
    Trams EG, Lauter CJ, Salem N Jr, Heine U 1981. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim. Biophys. Acta Biomembr. 645:63–70
    [Google Scholar]
  2. 2. 
    Gould SJ, Raposo G. 2013. As we wait: coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles 2:20389
    [Google Scholar]
  3. 3. 
    Thery C, Zitvogel L, Amigorena S 2002. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2:569–79
    [Google Scholar]
  4. 4. 
    Scott RE. 1976. Plasma membrane vesiculation: a new technique for isolation of plasma membranes. Science 194:743–45
    [Google Scholar]
  5. 5. 
    Bonucci E. 1967. Fine structure of early cartilage calcification. J. Ultrastruct. Res. 20:33–50
    [Google Scholar]
  6. 6. 
    Anderson HC. 1969. Vesicles associated with calcification in the matrix of epiphyseal cartilage. J. Cell Biol. 41:59–72
    [Google Scholar]
  7. 7. 
    Wolf P. 1967. The nature and significance of platelet products in human plasma. Br. J. Haematol. 13:269–88
    [Google Scholar]
  8. 8. 
    Bakhshian Nik A, Hutcheson JD, Aikawa E 2017. Extracellular vesicles as mediators of cardiovascular calcification. Front. Cardiovasc. Med. 4:78
    [Google Scholar]
  9. 9. 
    Anderson HC, Garimella R, Tague SE 2005. The role of matrix vesicles in growth plate development and biomineralization. Front. Biosci. 10:822–37
    [Google Scholar]
  10. 10. 
    Garnier D, Magnus N, Lee TH, Bentley V, Meehan B et al. 2012. Cancer cells induced to express mesenchymal phenotype release exosome-like extracellular vesicles carrying tissue factor. J. Biol. Chem. 287:43565–72
    [Google Scholar]
  11. 11. 
    Melki I, Tessandier N, Zufferey A, Boilard E 2017. Platelet microvesicles in health and disease. Platelets 28:214–21
    [Google Scholar]
  12. 12. 
    Arienti G, Carlini E, Verdacchi R, Cosmi EV, Palmerini CA 1997. Prostasome to sperm transfer of CD13/aminopeptidase N (EC 3.4.11.2). Biochim. Biophys. Acta Gen. Subj. 1336.533–38
    [Google Scholar]
  13. 13. 
    Stegmayr B, Brody I, Ronquist G 1982. A biochemical and ultrastructural study on the endogenous protein kinase activity of secretory granule membranes of prostatic origin in human seminal plasma. J. Ultrastruct. Res. 78:206–14
    [Google Scholar]
  14. 14. 
    Pan BT, Johnstone RM. 1983. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33:967–78
    [Google Scholar]
  15. 15. 
    Harding C, Heuser J, Stahl P 1983. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 97:329–39
    [Google Scholar]
  16. 16. 
    Bianchi E, Doe B, Goulding D, Wright GJ 2014. Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature 508:483–87
    [Google Scholar]
  17. 17. 
    Harding C, Heuser J, Stahl P 1984. Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur. J. Cell Biol. 35:256–63
    [Google Scholar]
  18. 18. 
    Frenette G, Sullivan R. 2001. Prostasome-like particles are involved in the transfer of P25b from the bovine epididymal fluid to the sperm surface. Mol. Reprod. Dev. 59:115–21
    [Google Scholar]
  19. 19. 
    Chernyshev VS, Rachamadugu R, Tseng YH, Belnap DM, Jia Y et al. 2015. Size and shape characterization of hydrated and desiccated exosomes. Anal. Bioanal. Chem. 407:3285–301
    [Google Scholar]
  20. 20. 
    Arraud N, Linares R, Tan S, Gounou C, Pasquet JM et al. 2014. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J. Thromb. Haemost. 12:614–27
    [Google Scholar]
  21. 21. 
    Sharma S, Das K, Woo J, Gimzewski JK 2014. Nanofilaments on glioblastoma exosomes revealed by peak force microscopy. J. R. Soc. Interface 11:20131150
    [Google Scholar]
  22. 22. 
    Booth AM, Fang Y, Fallon JK, Yang JM, Hildreth JE, Gould SJ 2006. Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J. Cell Biol. 172:923–35
    [Google Scholar]
  23. 23. 
    Golfetto O, Wakefield DL, Cacao EE, Avery KN, Kenyon V et al. 2018. A platform to enhance quantitative single molecule localization microscopy. J. Am. Chem. Soc. 140:12785–97
    [Google Scholar]
  24. 24. 
    Daaboul GG, Gagni P, Benussi L, Bettotti P, Ciani M et al. 2016. Digital detection of exosomes by interferometric imaging. Sci. Rep. 6:37246
    [Google Scholar]
  25. 25. 
    Morales-Kastresana A, Telford B, Musich TA, McKinnon K, Clayborne C et al. 2017. Labeling extracellular vesicles for nanoscale flow cytometry. Sci. Rep. 7:1878
    [Google Scholar]
  26. 26. 
    Nolan JP, Duggan E. 2018. Analysis of individual extracellular vesicles by flow cytometry. Methods Mol. Biol. 1678:79–92
    [Google Scholar]
  27. 27. 
    Claude A. 1943. The constitution of protoplasm. Science 97:451–56
    [Google Scholar]
  28. 28. 
    Sodar BW, Kittel A, Paloczi K, Vukman KV, Osteikoetxea X et al. 2016. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci. Rep. 6:24316
    [Google Scholar]
  29. 29. 
    Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z et al. 2018. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat. Cell Biol. 20:332–43
    [Google Scholar]
  30. 30. 
    Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV et al. 1996. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183:1161–72
    [Google Scholar]
  31. 31. 
    Fang Y, Wu N, Gan X, Yan W, Morrell JC, Gould SJ 2007. Higher-order oligomerization targets plasma membrane proteins and HIV Gag to exosomes. PLOS Biol 5:e158
    [Google Scholar]
  32. 32. 
    Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ 1998. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J. Biol. Chem. 273:20121–27
    [Google Scholar]
  33. 33. 
    Hemler ME. 2003. Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu. Rev. Cell Dev. Biol. 19:397–422
    [Google Scholar]
  34. 34. 
    Liang Y, Eng WS, Colquhoun DR, Dinglasan RR, Graham DR, Mahal LK 2014. Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment. J. Biol. Chem. 289:32526–37
    [Google Scholar]
  35. 35. 
    Segura E, Nicco C, Lombard B, Veron P, Raposo G et al. 2005. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood 106:216–23
    [Google Scholar]
  36. 36. 
    Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G et al. 2012. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14:677–85
    [Google Scholar]
  37. 37. 
    Rieu S, Geminard C, Rabesandratana H, Sainte-Marie J, Vidal M 2000. Exosomes released during reticulocyte maturation bind to fibronectin via integrin α4β1. Eur. J. Biochem. 267:583–90
    [Google Scholar]
  38. 38. 
    Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A et al. 2017. Pre-metastatic niches: organ-specific homes for metastases. Nat. Rev. Cancer 17:302–17
    [Google Scholar]
  39. 39. 
    Verweij FJ, van Eijndhoven MA, Hopmans ES, Vendrig T, Wurdinger T et al. 2011. LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation. EMBO J 30:2115–29
    [Google Scholar]
  40. 40. 
    Hurwitz SN, Nkosi D, Conlon MM, York SB, Liu X et al. 2017. CD63 regulates Epstein-Barr virus LMP1 exosomal packaging, enhancement of vesicle production, and noncanonical NF-κB signaling. J. Virol. 91:e02251–16
    [Google Scholar]
  41. 41. 
    van Dongen HM, Masoumi N, Witwer KW, Pegtel DM 2016. Extracellular vesicles exploit viral entry routes for cargo delivery. Microbiol. Mol. Biol. Rev. 80:369–86
    [Google Scholar]
  42. 42. 
    Arakelyan A, Fitzgerald W, Zicari S, Vanpouille C, Margolis L 2017. Extracellular vesicles carry HIV Env and facilitate HIV infection of human lymphoid tissue. Sci. Rep. 7:1695
    [Google Scholar]
  43. 43. 
    Masciopinto F, Giovani C, Campagnoli S, Galli-Stampino L, Colombatto P et al. 2004. Association of hepatitis C virus envelope proteins with exosomes. Eur. J. Immunol. 34:2834–42
    [Google Scholar]
  44. 44. 
    Nolte-’t Hoen E, Cremer T, Gallo RC, Margolis LB 2016. Extracellular vesicles and viruses: Are they close relatives?. PNAS 113:9155–61
    [Google Scholar]
  45. 45. 
    Gould SJ, Booth AM, Hildreth JE 2003. The Trojan exosome hypothesis. PNAS 100:10592–97
    [Google Scholar]
  46. 46. 
    Dewannieux M, Heidmann T. 2013. Endogenous retroviruses: acquisition, amplification and taming of genome invaders. Curr. Opin. Virol. 3:646–56
    [Google Scholar]
  47. 47. 
    Heidmann O, Beguin A, Paternina J, Berthier R, Deloger M et al. 2017. HEMO, an ancestral endogenous retroviral envelope protein shed in the blood of pregnant women and expressed in pluripotent stem cells and tumors. PNAS 114:E6642–51
    [Google Scholar]
  48. 48. 
    Dewannieux M, Harper F, Richaud A, Letzelter C, Ribet D et al. 2006. Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res 16:1548–56
    [Google Scholar]
  49. 49. 
    Vargas A, Zhou S, Ethier-Chiasson M, Flipo D, Lafond J et al. 2014. Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia. FASEB J 28:3703–19
    [Google Scholar]
  50. 50. 
    Kassiotis G, Stoye JP. 2017. Making a virtue of necessity: the pleiotropic role of human endogenous retroviruses in cancer. Philos. Trans. R. Soc. B 372:20160277
    [Google Scholar]
  51. 51. 
    Grow EJ, Flynn RA, Chavez SL, Bayless NL, Wossidlo M et al. 2015. Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells. Nature 522:221–25
    [Google Scholar]
  52. 52. 
    Buslei R, Strissel PL, Henke C, Schey R, Lang N et al. 2015. Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours. Neuropathol. Appl. Neurobiol. 41:180–200
    [Google Scholar]
  53. 53. 
    Denner J. 2016. Expression and function of endogenous retroviruses in the placenta. APMIS 124:31–43
    [Google Scholar]
  54. 54. 
    Denner J. 2014. The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and other retroviruses. AIDS 28:1081–90
    [Google Scholar]
  55. 55. 
    Chen G, Huang AC, Zhang W, Zhang G, Wu M et al. 2018. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 560:382–86
    [Google Scholar]
  56. 56. 
    Sargent I. 2013. Microvesicles and pre-eclampsia. Pregnancy Hypertens 3:58
    [Google Scholar]
  57. 57. 
    Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L et al. 2008. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 10:619–24
    [Google Scholar]
  58. 58. 
    Atay S, Banskota S, Crow J, Sethi G, Rink L, Godwin AK 2014. Oncogenic KIT-containing exosomes increase gastrointestinal stromal tumor cell invasion. PNAS 111:711–16
    [Google Scholar]
  59. 59. 
    Jarad M, Kuczynski EA, Morrison J, Viloria-Petit AM, Coomber BL 2017. Release of endothelial cell associated VEGFR2 during TGF-β modulated angiogenesis in vitro. BMC Cell Biol 18:10
    [Google Scholar]
  60. 60. 
    DeRita RM, Zerlanko B, Singh A, Lu H, Iozzo RV et al. 2017. c-Src, insulin-like growth factor I receptor, G-protein-coupled receptor kinases and focal adhesion kinase are enriched into prostate cancer cell exosomes. J. Cell Biochem. 118:66–73
    [Google Scholar]
  61. 61. 
    Blanchard N, Lankar D, Faure F, Regnault A, Dumont C et al. 2002. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex. J. Immunol. 168:3235–41
    [Google Scholar]
  62. 62. 
    Li M, Lu Y, Xu Y, Wang J, Zhang C et al. 2018. Horizontal transfer of exosomal CXCR4 promotes murine hepatocarcinoma cell migration, invasion and lymphangiogenesis. Gene 676:101–9
    [Google Scholar]
  63. 63. 
    Nager AR, Goldstein JS, Herranz-Perez V, Portran D, Ye F et al. 2017. An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling. Cell 168:252–63.e14
    [Google Scholar]
  64. 64. 
    Gonzalez-King H, Garcia NA, Ontoria-Oviedo I, Ciria M, Montero JA, Sepulveda P 2017. Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells 35:1747–59
    [Google Scholar]
  65. 65. 
    Sheldon H, Heikamp E, Turley H, Dragovic R, Thomas P et al. 2010. New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116:2385–94
    [Google Scholar]
  66. 66. 
    Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z 2011. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J. Immunol. 187:676–83
    [Google Scholar]
  67. 67. 
    Rabesandratana H, Toutant JP, Reggio H, Vidal M 1998. Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59) are released within exosomes during in vitro maturation of reticulocytes. Blood 91:2573–80
    [Google Scholar]
  68. 68. 
    Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST et al. 2015. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523:177–82
    [Google Scholar]
  69. 69. 
    Cheng L, Zhao W, Hill AF 2018. Exosomes and their role in the intercellular trafficking of normal and disease associated prion proteins. Mol. Asp. Med. 60:62–68
    [Google Scholar]
  70. 70. 
    Qi J, Zhou Y, Jiao Z, Wang X, Zhao Y et al. 2017. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth through hedgehog signaling pathway. Cell Physiol. Biochem. 42:2242–54
    [Google Scholar]
  71. 71. 
    Gross JC, Zelarayan LC. 2018. The mingle-mangle of Wnt signaling and extracellular vesicles: functional implications for heart research. Front. Cardiovasc. Med. 5:10
    [Google Scholar]
  72. 72. 
    Liu M, Sun Y, Zhang Q 2018. Emerging role of extracellular vesicles in bone remodeling. J. Dent. Res. 97:859–68
    [Google Scholar]
  73. 73. 
    Borges FT, Melo SA, Ozdemir BC, Kato N, Revuelta I et al. 2013. TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J. Am. Soc. Nephrol. 24:385–92
    [Google Scholar]
  74. 74. 
    Sampey GC, Saifuddin M, Schwab A, Barclay R, Punya S et al. 2016. Exosomes from HIV-1-infected cells stimulate production of pro-inflammatory cytokines through trans-activating response (TAR) RNA. J. Biol. Chem. 291:1251–66
    [Google Scholar]
  75. 75. 
    Munich S, Sobo-Vujanovic A, Buchser WJ, Beer-Stolz D, Vujanovic NL 2012. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology 1:1074–83
    [Google Scholar]
  76. 76. 
    Kim SH, Bianco NR, Shufesky WJ, Morelli AE, Robbins PD 2007. MHC class II+ exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J. Immunol. 179:2235–41
    [Google Scholar]
  77. 77. 
    McGough IJ, Vincent JP. 2016. Exosomes in developmental signalling. Development 143:2482–93
    [Google Scholar]
  78. 78. 
    Atay S, Gercel-Taylor C, Taylor DD 2011. Human trophoblast-derived exosomal fibronectin induces pro-inflammatory IL-1β production by macrophages. Am. J. Reprod. Immunol. 66:259–69
    [Google Scholar]
  79. 79. 
    Zheng J, Hernandez JM, Doussot A, Bojmar L, Zambirinis CP et al. 2018. Extracellular matrix proteins and carcinoembryonic antigen-related cell adhesion molecules characterize pancreatic duct fluid exosomes in patients with pancreatic cancer. HPB 20:597–604
    [Google Scholar]
  80. 80. 
    Santasusagna S, Moreno I, Navarro A, Castellano JJ, Martinez F et al. 2018. Proteomic analysis of liquid biopsy from tumor-draining vein indicates that high expression of exosomal ECM1 is associated with relapse in stage I-III colon cancer. Transl. Oncol. 11:715–21
    [Google Scholar]
  81. 81. 
    Oshima K, Aoki N, Kato T, Kitajima K, Matsuda T 2002. Secretion of a peripheral membrane protein, MFG-E8, as a complex with membrane vesicles. Eur. J. Biochem. 269:1209–18
    [Google Scholar]
  82. 82. 
    Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ et al. 2013. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol. Cell Proteom. 12:343–55
    [Google Scholar]
  83. 83. 
    Hsu C, Morohashi Y, Yoshimura S, Manrique-Hoyos N, Jung S et al. 2010. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C. J. Cell Biol. 189:223–32
    [Google Scholar]
  84. 84. 
    Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G et al. 2010. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12:19–30
    [Google Scholar]
  85. 85. 
    Subramanian RP, Wildschutte JH, Russo C, Coffin JM 2011. Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses. Retrovirology 8:90
    [Google Scholar]
  86. 86. 
    Gerber PP, Cabrini M, Jancic C, Paoletti L, Banchio C et al. 2015. Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate. J. Cell Biol. 209:435–52
    [Google Scholar]
  87. 87. 
    Ashley J, Cordy B, Lucia D, Fradkin LG, Budnik V, Thomson T 2018. Retrovirus-like Gag protein Arc1 binds RNA and traffics across synaptic boutons. Cell 172:262–74.e11
    [Google Scholar]
  88. 88. 
    Pastuzyn ED, Day CE, Kearns RB, Kyrke-Smith M, Taibi AV et al. 2018. The neuronal gene Arc encodes a repurposed retrotransposon Gag protein that mediates intercellular RNA transfer. Cell 172:275–88.e18
    [Google Scholar]
  89. 89. 
    Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W et al. 2003. Proteomic and biochemical analyses of human B cell-derived exosomes: potential implications for their function and multivesicular body formation. J. Biol. Chem. 278:10963–72
    [Google Scholar]
  90. 90. 
    Shen B, Fang Y, Wu N, Gould SJ 2011. Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein-sorting pathway. J. Biol. Chem. 286:44162–76
    [Google Scholar]
  91. 91. 
    Hegmans JP, Bard MP, Hemmes A, Luider TM, Kleijmeer MJ et al. 2004. Proteomic analysis of exosomes secreted by human mesothelioma cells. Am. J. Pathol. 164:1807–15
    [Google Scholar]
  92. 92. 
    Bretscher A, Chambers D, Nguyen R, Reczek D 2000. ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Annu. Rev. Cell Dev. Biol. 16:113–43
    [Google Scholar]
  93. 93. 
    Pisitkun T, Shen RF, Knepper MA 2004. Identification and proteomic profiling of exosomes in human urine. PNAS 101:13368–73
    [Google Scholar]
  94. 94. 
    Nakamura K, Sawada K, Kinose Y, Yoshimura A, Toda A et al. 2017. Exosomes promote ovarian cancer cell invasion through transfer of CD44 to peritoneal mesothelial cells. Mol. Cancer Res. 15:78–92
    [Google Scholar]
  95. 95. 
    Melo SA, Sugimoto H, O'Connell JT, Kato N, Villanueva A et al. 2014. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26:707–21
    [Google Scholar]
  96. 96. 
    Latysheva N, Muratov G, Rajesh S, Padgett M, Hotchin NA et al. 2006. Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63. Mol. Cell Biol. 26:7707–18
    [Google Scholar]
  97. 97. 
    Friand V, David G, Zimmermann P 2015. Syntenin and syndecan in the biogenesis of exosomes. Biol. Cell 107:331–41
    [Google Scholar]
  98. 98. 
    Chatellard-Causse C, Blot B, Cristina N, Torch S, Missotten M, Sadoul R 2002. Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization. J. Biol. Chem. 277:29108–15
    [Google Scholar]
  99. 99. 
    Henne WM, Buchkovich NJ, Emr SD 2011. The ESCRT pathway. Dev. Cell 21:77–91
    [Google Scholar]
  100. 100. 
    Radulovic M, Stenmark H. 2018. ESCRTs in membrane sealing. Biochem. Soc. Trans. 46:773–78
    [Google Scholar]
  101. 101. 
    Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D et al. 2008. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–47
    [Google Scholar]
  102. 102. 
    Colombo M, Moita C, van Niel G, Kowal J, Vigneron J et al. 2013. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 126:5553–65
    [Google Scholar]
  103. 103. 
    Banfer S, Schneider D, Dewes J, Strauss MT, Freibert SA et al. 2018. Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion. PNAS 115:E4396–405
    [Google Scholar]
  104. 104. 
    Nabhan JF, Hu R, Oh RS, Cohen SN, Lu Q 2012. Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. PNAS 109:4146–51
    [Google Scholar]
  105. 105. 
    Putz U, Howitt J, Lackovic J, Foot N, Kumar S et al. 2008. Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins. J. Biol. Chem. 283:32621–27
    [Google Scholar]
  106. 106. 
    Cheng Y, Schorey JS. 2016. Targeting soluble proteins to exosomes using a ubiquitin tag. Biotechnol. Bioeng. 113:1315–24
    [Google Scholar]
  107. 107. 
    Alderson TR, Kim JH, Markley JL 2016. Dynamical structures of Hsp70 and Hsp70-Hsp40 complexes. Structure 24:1014–30
    [Google Scholar]
  108. 108. 
    Mathew A, Bell A, Johnstone RM 1995. Hsp-70 is closely associated with the transferrin receptor in exosomes from maturing reticulocytes. Biochem. J. 308:Part 3823–30
    [Google Scholar]
  109. 109. 
    Reddy VS, Madala SK, Trinath J, Reddy GB 2018. Extracellular small heat shock proteins: exosomal biogenesis and function. Cell Stress Chaperones 23:441–54
    [Google Scholar]
  110. 110. 
    Takeuchi T, Suzuki M, Fujikake N, Popiel HA, Kikuchi H et al. 2015. Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level. PNAS 112:E2497–506
    [Google Scholar]
  111. 111. 
    Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G et al. 2001. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 166:7309–18
    [Google Scholar]
  112. 112. 
    Li J, Chen X, Yi J, Liu Y, Li D et al. 2016. Identification and characterization of 293T cell-derived exosomes by profiling the protein, mRNA and microRNA components. PLOS ONE 11:e0163043
    [Google Scholar]
  113. 113. 
    Rilla K, Pasonen-Seppanen S, Deen AJ, Koistinen VV, Wojciechowski S et al. 2013. Hyaluronan production enhances shedding of plasma membrane-derived microvesicles. Exp. Cell Res. 319:2006–18
    [Google Scholar]
  114. 114. 
    Thompson CA, Purushothaman A, Ramani VC, Vlodavsky I, Sanderson RD 2013. Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes. J. Biol. Chem. 288:10093–99
    [Google Scholar]
  115. 115. 
    Ronquist KG, Ek B, Stavreus-Evers A, Larsson A, Ronquist G 2013. Human prostasomes express glycolytic enzymes with capacity for ATP production. Am. J. Physiol. Endocrinol. Metab. 304:E576–82
    [Google Scholar]
  116. 115a. 
    Basso M, Bonetto A 2016. Extracellular vesicles and a novel form of communication in the brain. Front. Neurosci.10–127 https://doi.org/10.3389/fnins.2016.00127
    [Crossref] [Google Scholar]
  117. 116. 
    Ridder K, Sevko A, Heide J, Dams M, Rupp AK et al. 2015. Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment. Oncoimmunology 4:e1008371
    [Google Scholar]
  118. 117. 
    Lai CP, Kim EY, Badr CE, Weissleder R, Mempel TR et al. 2015. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat. Commun. 6:7029
    [Google Scholar]
  119. 118. 
    Yim N, Ryu SW, Choi K, Lee KR, Lee S et al. 2016. Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein–protein interaction module. Nat. Commun. 7:12277
    [Google Scholar]
  120. 119. 
    Gould S, Fordjour FK, Daaboul G 2019. A shared pathway of exosome biogenesis operates at plasma and endosome membranes. bioRxiv 545228. https://doi.org/10.1101/545228
    [Crossref]
  121. 120. 
    Raj A, van Oudenaarden A 2008. Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135:216–26
    [Google Scholar]
  122. 121. 
    Battich N, Stoeger T, Pelkmans L 2015. Control of transcript variability in single mammalian cells. Cell 163:1596–610
    [Google Scholar]
  123. 122. 
    Batista BS, Eng WS, Pilobello KT, Hendricks-Munoz KD, Mahal LK 2011. Identification of a conserved glycan signature for microvesicles. J. Proteome Res. 10:4624–33
    [Google Scholar]
  124. 123. 
    Shimoda A, Tahara Y, Sawada SI, Sasaki Y, Akiyoshi K 2017. Glycan profiling analysis using evanescent-field fluorescence-assisted lectin array: importance of sugar recognition for cellular uptake of exosomes from mesenchymal stem cells. Biochem. Biophys. Res. Commun. 491:701–7
    [Google Scholar]
  125. 124. 
    Skotland T, Sandvig K, Llorente A 2017. Lipids in exosomes: current knowledge and the way forward. Prog. Lipid Res. 66:30–41
    [Google Scholar]
  126. 125. 
    Llorente A, Skotland T, Sylvänne T, Kauhanen D, Róg T et al. 2013. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1831:1302–9
    [Google Scholar]
  127. 126. 
    Dillon SR, Mancini M, Rosen A, Schlissel MS 2000. Annexin V binds to viable B cells and colocalizes with a marker of lipid rafts upon B cell receptor activation. J. Immunol. 164:1322–32
    [Google Scholar]
  128. 127. 
    Bette-Bobillo P, Vidal M. 1995. Characterization of phospholipase A2 activity in reticulocyte endocytic vesicles. Eur. J. Biochem. 228:199–205
    [Google Scholar]
  129. 128. 
    Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R et al. 2006. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20:847–56
    [Google Scholar]
  130. 129. 
    Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9:654–59
    [Google Scholar]
  131. 130. 
    Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L et al. 2008. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 10:1470–76
    [Google Scholar]
  132. 131. 
    Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES et al. 2010. Functional delivery of viral miRNAs via exosomes. PNAS 107:6328–33
    [Google Scholar]
  133. 132. 
    Wei Z, Batagov AO, Schinelli S, Wang J, Wang Y et al. 2017. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat. Commun. 8:1145
    [Google Scholar]
  134. 133. 
    Shurtleff MJ, Yao J, Qin Y, Nottingham RM, Temoche-Diaz MM et al. 2017. Broad role for YBX1 in defining the small noncoding RNA composition of exosomes. PNAS 114:E8987–95
    [Google Scholar]
  135. 134. 
    Koppers-Lalic D, Hackenberg M, Bijnsdorp IV, van Eijndhoven MAJ, Sadek P et al. 2014. Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep 8:1649–58
    [Google Scholar]
  136. 135. 
    Baglio SR, van Eijndhoven MA, Koppers-Lalic D, Berenguer J, Lougheed SM et al. 2016. Sensing of latent EBV infection through exosomal transfer of 5′pppRNA. PNAS 113:E587–96
    [Google Scholar]
  137. 136. 
    Giraldez MD, Spengler RM, Etheridge A, Godoy PM, Barczak AJ et al. 2018. Comprehensive multi-center assessment of small RNA-seq methods for quantitative miRNA profiling. Nat. Biotechnol. 36:746–57
    [Google Scholar]
  138. 137. 
    McKenzie AJ, Hoshino D, Hong NH, Cha DJ, Franklin JL et al. 2016. KRAS-MEK signaling controls Ago2 sorting into exosomes. Cell Rep 15:978–87
    [Google Scholar]
  139. 138. 
    Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F, Perez-Hernandez D, Vazquez J et al. 2013. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 4:2980
    [Google Scholar]
  140. 139. 
    Santangelo L, Giurato G, Cicchini C, Montaldo C, Mancone C et al. 2016. The RNA-binding protein SYNCRIP is a component of the hepatocyte exosomal machinery controlling microRNA sorting. Cell Rep 17:799–808
    [Google Scholar]
  141. 140. 
    Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R 2016. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife 5:e19276
    [Google Scholar]
  142. 141. 
    Teng Y, Ren Y, Hu X, Mu J, Samykutty A et al. 2017. MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression. Nat. Commun. 8:14448
    [Google Scholar]
  143. 142. 
    Mukherjee K, Ghoshal B, Ghosh S, Chakrabarty Y, Shwetha S et al. 2016. Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response. EMBO Rep 17:1184–203
    [Google Scholar]
  144. 143. 
    Telesnitsky A, Wolin SL. 2016. The host RNAs in retroviral particles. Viruses 8:235
    [Google Scholar]
  145. 144. 
    Verweij FJ, Bebelman MP, Jimenez CR, Garcia-Vallejo JJ, Janssen H et al. 2018. Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling. J. Cell Biol. 217:1129–42
    [Google Scholar]
  146. 145. 
    Balaj L, Lessard R, Dai L, Cho YJ, Pomeroy SL et al. 2011. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat. Commun. 2:180
    [Google Scholar]
  147. 146. 
    Kahlert C, Melo SA, Protopopov A, Tang J, Seth S et al. 2014. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J. Biol. Chem. 289:3869–75
    [Google Scholar]
  148. 147. 
    Thakur BK, Zhang H, Becker A, Matei I, Huang Y et al. 2014. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 24:766–69
    [Google Scholar]
  149. 148. 
    Sansone P, Savini C, Kurelac I, Chang Q, Amato LB et al. 2017. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. PNAS 114:E9066–75
    [Google Scholar]
  150. 149. 
    Colombo M, Raposo G, Théry C 2014. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30:255–89
    [Google Scholar]
  151. 150. 
    Hyenne V, Apaydin A, Rodriguez D, Spiegelhalter C, Hoff-Yoessle S et al. 2015. RAL-1 controls multivesicular body biogenesis and exosome secretion. J. Cell Biol. 211:27–37
    [Google Scholar]
  152. 151. 
    Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM 2015. Directional cell movement through tissues is controlled by exosome secretion. Nat. Commun. 6:7164
    [Google Scholar]
  153. 152. 
    Casado S, Lobo M, Paino CL 2017. Dynamics of plasma membrane surface related to the release of extracellular vesicles by mesenchymal stem cells in culture. Sci. Rep. 7:6767
    [Google Scholar]
  154. 153. 
    Cantaluppi V, Gatti S, Medica D, Figliolini F, Bruno S et al. 2012. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia–reperfusion injury by microRNA-dependent reprogramming of resident renal cells. Kidney Int 82:412–27
    [Google Scholar]
  155. 154. 
    Shen B, Wu N, Yang JM, Gould SJ 2011. Protein targeting to exosomes/microvesicles by plasma membrane anchors. J. Biol. Chem. 286:14383–95
    [Google Scholar]
  156. 155. 
    Shao H, Chung J, Balaj L, Charest A, Bigner DD et al. 2012. Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat. Med. 18:1835–40
    [Google Scholar]
  157. 156. 
    Wehman AM, Poggioli C, Schweinsberg P, Grant BD, Nance J 2011. The P4-ATPase TAT-5 inhibits the budding of extracellular vesicles in C. elegans embryos. Curr. Biol. 21:1951–59
    [Google Scholar]
  158. 157. 
    Welsch S, Keppler OT, Habermann A, Allespach I, Krijnse-Locker J, Krausslich HG 2007. HIV-1 buds predominantly at the plasma membrane of primary human macrophages. PLOS Pathog 3:e36
    [Google Scholar]
  159. 158. 
    Egea-Jimenez AL, Zimmermann P. 2018. Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles. J. Lipid Res. 59:1554–60
    [Google Scholar]
  160. 159. 
    Deneka M, Pelchen-Matthews A, Byland R, Ruiz-Mateos E, Marsh M 2007. In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53. J. Cell Biol. 177:329–41
    [Google Scholar]
  161. 160. 
    Nkwe DO, Pelchen-Matthews A, Burden JJ, Collinson LM, Marsh M 2016. The intracellular plasma membrane-connected compartment in the assembly of HIV-1 in human macrophages. BMC Biol 14:50
    [Google Scholar]
  162. 161. 
    Edgar JR, Manna PT, Nishimura S, Banting G, Robinson MS 2016. Tetherin is an exosomal tether. eLife 5:e17180
    [Google Scholar]
  163. 162. 
    Neil SJ, Zang T, Bieniasz PD 2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425–30
    [Google Scholar]
  164. 163. 
    Blobel G. 1995. Unidirectional and bidirectional protein traffic across membranes. Cold Spring Harb. Symp. Quant. Biol. 60:1–10
    [Google Scholar]
  165. 164. 
    de Petris S, Raff MC 1973. Normal distribution, patching and capping of lymphocyte surface immunoglobulin studied by electron microscopy. Nat. New Biol. 241:257–59
    [Google Scholar]
  166. 165. 
    Fevrier B, Vilette D, Archer F, Loew D, Faigle W et al. 2004. Cells release prions in association with exosomes. PNAS 101:9683–88
    [Google Scholar]
  167. 166. 
    Vidal M, Mangeat P, Hoekstra D 1997. Aggregation reroutes molecules from a recycling to a vesicle-mediated secretion pathway during reticulocyte maturation. J. Cell Sci. 110:Part 161867–77
    [Google Scholar]
  168. 167. 
    Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z 2005. Induction of heat shock proteins in B-cell exosomes. J. Cell Sci. 118:3631–38
    [Google Scholar]
  169. 168. 
    Briggs JA, Simon MN, Gross I, Krausslich HG, Fuller SD et al. 2004. The stoichiometry of Gag protein in HIV-1. Nat. Struct. Mol. Biol. 11:672–75
    [Google Scholar]
  170. 168a. 
    Snead WT, Hayden CC, Gadok AK, Zhao C, Lafer EM et al. 2017. Membrane fission by protein crowding. PNAS 114:3258–67
    [Google Scholar]
  171. 169. 
    Gan X, Gould SJ. 2011. Identification of an inhibitory budding signal that blocks the release of HIV particles and exosome/microvesicle proteins. Mol. Biol. Cell. 22:817–30
    [Google Scholar]
  172. 170. 
    Ogretmen B. 2018. Sphingolipid metabolism in cancer signalling and therapy. Nat. Rev. Cancer 18:33–50
    [Google Scholar]
  173. 171. 
    Lingwood D, Simons K. 2010. Lipid rafts as a membrane-organizing principle. Science 327:46–50
    [Google Scholar]
  174. 172. 
    Sevcsik E, Brameshuber M, Folser M, Weghuber J, Honigmann A, Schutz GJ 2015. GPI-anchored proteins do not reside in ordered domains in the live cell plasma membrane. Nat. Commun. 6:6969
    [Google Scholar]
  175. 173. 
    Munro S. 2003. Lipid rafts: Elusive or illusive?. Cell 115:377–88
    [Google Scholar]
  176. 174. 
    Nguyen DG, Booth A, Gould SJ, Hildreth JE 2003. Evidence that HIV budding in primary macrophages occurs through the exosome release pathway. J. Biol. Chem. 278:52347–54
    [Google Scholar]
  177. 175. 
    Zhen Y, Stenmark H. 2015. Cellular functions of Rab GTPases at a glance. J Cell Sci 128:3171–76
    [Google Scholar]
  178. 176. 
    Klinkert K, Echard A. 2016. Rab35 GTPase: a central regulator of phosphoinositides and F-actin in endocytic recycling and beyond. Traffic 17:1063–77
    [Google Scholar]
  179. 177. 
    Savina A, Vidal M, Colombo MI 2002. The exosome pathway in K562 cells is regulated by Rab11. J. Cell Sci. 115:2505–15
    [Google Scholar]
  180. 178. 
    Savina A, Fader CM, Damiani MT, Colombo MI 2005. Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner. Traffic 6:131–43
    [Google Scholar]
  181. 179. 
    Messenger SW, Woo SS, Sun Z, Martin TFJ 2018. A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4. J. Cell Biol. 217:2877–90
    [Google Scholar]
  182. 180. 
    Ghossoub R, Lembo F, Rubio A, Gaillard CB, Bouchet J et al. 2014. Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Nat. Commun. 5:3477
    [Google Scholar]
  183. 181. 
    Guo H, Chitiprolu M, Roncevic L, Javalet C, Hemming FJ et al. 2017. Atg5 disassociates the V1V0-ATPase to promote exosome production and tumor metastasis independent of canonical macroautophagy. Dev. Cell 43:716–30.e7
    [Google Scholar]
  184. 182. 
    Abdulrahman BA, Abdelaziz DH, Schatzl HM 2018. Autophagy regulates exosomal release of prions in neuronal cells. J. Biol. Chem. 293:8956–68
    [Google Scholar]
  185. 183. 
    Thomas RE, Vincow ES, Merrihew GE, MacCoss MJ, Davis MY, Pallanck LJ 2018. Glucocerebrosidase deficiency promotes protein aggregation through dysregulation of extracellular vesicles. PLOS Genet 14:e1007694
    [Google Scholar]
  186. 184. 
    Melikyan GB. 2014. HIV entry: A game of hide-and-fuse. ? Curr. Opin. Virol. 4:1–7
    [Google Scholar]
  187. 185. 
    Mulcahy LA, Pink RC, Carter DR 2014. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles 3:24641
    [Google Scholar]
  188. 186. 
    Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S 2007. Identification of Tim4 as a phosphatidylserine receptor. Nature 450:435–39
    [Google Scholar]
  189. 187. 
    Fraschilla I, Pillai S. 2017. Viewing Siglecs through the lens of tumor immunology. Immunol. Rev. 276:178–91
    [Google Scholar]
  190. 188. 
    Yoon S, Kovalenko A, Bogdanov K, Wallach D 2017. MLKL, the protein that mediates necroptosis, also regulates endosomal trafficking and extracellular vesicle generation. Immunity 47:51–65.e7
    [Google Scholar]
  191. 189. 
    Nabet BY, Qiu Y, Shabason JE, Wu TJ, Yoon T et al. 2017. Exosome RNA unshielding couples stromal activation to pattern recognition receptor signaling in cancer. Cell 170:352–66.e13
    [Google Scholar]
  192. 190. 
    Quek C, Hill AF. 2017. The role of extracellular vesicles in neurodegenerative diseases. Biochem. Biophys. Res. Commun. 483:1178–86
    [Google Scholar]
  193. 191. 
    Verweij FJ, de Heus C, Kroeze S, Cai H, Kieff E et al. 2015. Exosomal sorting of the viral oncoprotein LMP1 is restrained by TRAF2 association at signalling endosomes. J. Extracell. Vesicles 4:26334
    [Google Scholar]
  194. 192. 
    Rak J. 2010. Microparticles in cancer. Semin. Thromb. Hemost. 36:888–906
    [Google Scholar]
  195. 193. 
    Subra C, Grand D, Laulagnier K, Stella A, Lambeau G et al. 2010. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J. Lipid Res. 51:2105–20
    [Google Scholar]
  196. 194. 
    Theodoraki MN, Yerneni SS, Hoffmann TK, Gooding WE, Whiteside TL 2018. Clinical significance of PD-L1+ exosomes in plasma of head and neck cancer patients. Clin. Cancer Res. 24:896–905
    [Google Scholar]
  197. 195. 
    Monypenny J, Milewicz H, Flores-Borja F, Weitsman G, Cheung A et al. 2018. ALIX regulates tumor-mediated immunosuppression by controlling EGFR activity and PD-L1 presentation. Cell Rep 24:630–41
    [Google Scholar]
  198. 196. 
    Delorme-Axford E, Donker RB, Mouillet JF, Chu T, Bayer A et al. 2013. Human placental trophoblasts confer viral resistance to recipient cells. PNAS 110:12048–53
    [Google Scholar]
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