TitleExosomes from Osteosarcoma and normal osteoblast differ in proteomic cargo and immunomodulatory effects on T cells.
Publication TypeJournal Article
Year of Publication2017
AuthorsTroyer, RM, Ruby, CE, Goodall, CP, Yang, L, Maier, CS, Albarqi, HA, Brady, JV, Bathke, K, Taratula, O, Mourich, D, Bracha, S
JournalExp Cell Res
Volume358
Issue2
Pagination369-376
Date Published2017 09 15
ISSN1090-2422
KeywordsAnimals, Cell Proliferation, Dogs, Exosomes, Flow Cytometry, Lymphocyte Activation, Osteoblasts, Osteosarcoma, Proteomics, T-Lymphocytes, Transforming Growth Factor beta
Abstract

BACKGROUND: Canine osteosarcoma (OSA) is the most common cancer of the appendicular skeleton and is associated with high metastatic rate to the lungs and poor prognosis. Recent studies have shown the impact of malignant-derived exosomes on immune cells and the facilitation of immune evasion. In the current study, we have characterized the proteomic profile of exosomes derived from healthy osteoblasts and osteosarcoma cell lines. We investigated the direct impact of these exosomes on healthy T cells.

RESULTS: Proteomic cargo of the malignant exosomes was markedly different from osteoblastic exosomes and contained immunosuppressive proteins including TGF-β, α fetoprotein and heat shock proteins. OSA exosomes directly attenuated the rate of T cell proliferation, increased a regulatory (FoxP3+) CD4+ phenotype and diminished the expression of the activation marker CD25+ on CD8+ cells. Exosomes of osteoblasts also demonstrated a direct impact on T cells, but to a lesser degree.

CONCLUSIONS: Osteosarcoma-derived exosomes compared to normal osteoblasts contain an immunomodulatory cargo, which reduced the rate of T cell proliferation and promoted T regulatory phenotype. Osteoblast-derived exosomes can also reduce T cell activity, but to lesser degree compared to OSA exosomes and without promoting a T regulatory phenotype.

DOI10.1016/j.yexcr.2017.07.011
Alternate JournalExp. Cell Res.
PubMed ID28712929