Exosomes from Osteosarcoma and normal osteoblast differ in proteomic cargo and immunomodulatory effects on T cells
Journal Article
·
· Experimental Cell Research
- Department of Chemistry, College of Science, Oregon State University, Corvallis, OR (United States)
- Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR (United States)
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR (United States)
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. - Highlights: • Proteomic profiles of osteoblasts and osteosarcoma exosomes have been characterized. • Malignant exosomes have immunosuppressive phenotype. • Osteosarcoma exosomes inhibit CD4{sup +} and CD8{sup +} T cell proliferation and activation. • Osteosarcoma exosomes can upregulate the expression of FOXP3 and CD25{sup +} in CD4{sup +} T cells.
- OSTI ID:
- 22738161
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 358; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
Similar Records
Regulatory T cells generated during cytomegalovirus in vitro stimulation of mononuclear cells from HIV-infected individuals on HAART correlate with decreased lymphocyte proliferation
An upregulation of CD8{sup +}CD25{sup +}Foxp3{sup +} T cells with suppressive function through interleukin 2 pathway in pulmonary arterial hypertension
Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma
Journal Article
·
Fri Sep 01 00:00:00 EDT 2006
· Virology
·
OSTI ID:20850555
An upregulation of CD8{sup +}CD25{sup +}Foxp3{sup +} T cells with suppressive function through interleukin 2 pathway in pulmonary arterial hypertension
Journal Article
·
Fri Sep 15 00:00:00 EDT 2017
· Experimental Cell Research
·
OSTI ID:22738154
Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma
Journal Article
·
Fri Aug 16 00:00:00 EDT 2013
· Biochemical and Biophysical Research Communications
·
OSTI ID:22242054