Melanoma cell-derived exosomes alter macrophage and dendritic cell functions in vitro.
To clarify controversies in the literature of the field, we have purified and characterized B16F1 melanoma cell derived exosomes (mcd-exosomes) then we attempted to dissect their immunological activities. We tested how mcd-exosomes influence CD4+ T cell proliferation induced by bone marrow derived dendritic cells; we quantified NF-κB activation in mature macrophages stimulated with mcd-exosomes, and we compared the cytokine profile of LPS-stimulated, IL-4 induced, and mcd-exosome treated macrophages. We observed that mcd-exosomes helped the maturation of dendritic cells, enhancing T cell proliferation induced by the treated dendritic cells. The exosomes also activated macrophages, as measured by NF-κB activation. The cytokine and chemokine profile of macrophages treated with tumor cell derived exosomes showed marked differences from those induced by either LPS or IL-4, and it suggested that exosomes may play a role in the tumor progression and metastasis formation through supporting tumor immune escape mechanisms.
Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
Annamaria
A
Marton
Csaba
C
Vizler
Erzsebet
E
Kusz
Viktoria
V
Temesfoi
Zsuzsa
Z
Szathmary
Krisztina
K
Nagy
Zsolt
Z
Szegletes
Gyorgy
G
Varo
Laszlo
L
Siklos
Robert L
RL
Katona
Vilmos
V
Tubak
O M Zack
OM
Howard
Erno
E
Duda
Janos
J
Minarovits
Katalin
K
Nagy
Krisztina
K
Buzas
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D055354:Exosomes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D015847:Interleukin-4