Exosomes from Osteosarcoma and normal osteoblast differ in proteomic cargo and immunomodulatory effects on T cells

• Published in: Experimental cell research 2017-09, Vol.358 (2), p.369-376
• Main Authors: Troyer, Ryan M., Ruby, Carl E., Goodall, Cheri P., Yang, Liping, Maier, Claudia S., Albarqi, Hassan A., Brady, Jacqueline V., Bathke, Kallan, Taratula, Oleh, Mourich, Dan, Bracha, Shay
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Canine; CELL PROLIFERATION; Cell Proliferation - physiology; CONNECTIVE TISSUE CELLS; Dogs; Exosome; Exosomes - metabolism; Flow Cytometry - methods; GROWTH FACTORS; HEAT-SHOCK PROTEINS; Lymphocyte Activation - immunology; Osteoblast; Osteoblasts - metabolism; Osteosarcoma; Osteosarcoma - metabolism; OSTEOSARCOMAS; PHENOTYPE; Proteomic; Proteomics; RATS; T regulatory; T-Lymphocytes - immunology; Transforming Growth Factor beta - metabolism
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2017.07.011

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. 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. 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. •Proteomic profiles of osteoblasts and osteosarcoma exosomes have been characterized.•Malignant exosomes have immunosuppressive phenotype.•Osteosarcoma exosomes inhibit CD4+ and CD8+ T cell proliferation and activation.•Osteosarcoma exosomes can upregulate the expression of FOXP3 and CD25+ in CD4+ T cells.