Ryan M Troyer1, Carl E Ruby2, Cheri P Goodall3, Liping Yang4, Claudia S Maier5, Hassan A Albarqi6, Jacqueline V Brady7, Kallan Bathke8, Oleh Taratula9, Dan Mourich10, Shay Bracha11. 1. Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA; Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA. Electronic address: Ryan.Troyer@oregonstate.edu. 2. Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA; Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA. Electronic address: carl.ruby@yahoo.com. 3. Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA. Electronic address: Cheri.Goodall@oregonstate.edu. 4. Department of Chemistry, College of Science, Oregon State University, Corvallis, OR, USA. Electronic address: yangli@science.oregonstate.edu. 5. Department of Chemistry, College of Science, Oregon State University, Corvallis, OR, USA. Electronic address: claudia.maier@oregonstate.edu. 6. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA. Electronic address: albarqih@oregonstate.edu. 7. Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA. Electronic address: Jackie.Brady@oregonstate.edu. 8. Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA. Electronic address: bathke1993@gmail.com. 9. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA. Electronic address: Oleh.Taratula@oregonstate.edu. 10. Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA. Electronic address: dmourich@me.com. 11. Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA. Electronic address: shay.bracha@oregonstate.edu.
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.
BACKGROUND:Canineosteosarcoma (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.
Authors: Kelly M Makielski; Alicia J Donnelly; Ali Khammanivong; Milcah C Scott; Andrea R Ortiz; Dana C Galvan; Hirotaka Tomiyasu; Clarissa Amaya; Kristin A Ward; Alexa Montoya; John R Garbe; Lauren J Mills; Gary R Cutter; Joelle M Fenger; William C Kisseberth; Timothy D O'Brien; Brenda J Weigel; Logan G Spector; Brad A Bryan; Subbaya Subramanian; Jaime F Modiano Journal: Lab Invest Date: 2021-09-06 Impact factor: 5.662
Authors: Jacqueline V Brady; Ryan M Troyer; Stephen A Ramsey; Haley Leeper; Liping Yang; Claudia S Maier; Cheri P Goodall; Carl E Ruby; Hassan A M Albarqi; Oleh Taratula; Shay Bracha Journal: Transl Oncol Date: 2018-07-24 Impact factor: 4.243