Journal of Blood Medicine (May 2021)
Murine Leukemia-Derived Extracellular Vesicles Elicit Antitumor Immune Response
Abstract
Alejandro Pando, Loren Fast, Patrycja M Dubielecka, Anna Chorzalska, Sicheng Wen, John Reagan Division of Hematology/Oncology, Department of Medicine, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, Providence, RI, USACorrespondence: Loren FastDivision of Hematology/Oncology, Department of Medicine, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, 31 S Killingly Road, Foster, RI, 02825, USATel +1 401 533-8658Email [email protected]: Extracellular vesicles (EVs) are heterogeneous lipid bilayer particles secreted by cells. EVs contain proteins, RNA, DNA and other cargo that can have immunomodulatory effects. Cancer-derived EVs have been described as having immunomodulating effects in vivo with immunosuppressive and pro-tumor growth capabilities. However, cancer-derived EVs have also been harnessed and utilized for anti-cancer potential.Methods: To assess the immunomodulatory effect of EVs produced by acute myeloid leukemia (AML) cells, we isolated vesicles secreted by the murine AML cell line, C1498, and investigated their effect on in vitro and in vivo immune responses.Results: These leukemia-derived EVs were found to induce increased proliferation of CD3+ cells and enhanced cytolytic activity of CD3+ cells directed toward leukemic cells in vitro. Injection of leukemia-derived EVs into syngeneic naïve mice induced T cell responses in vivo and resulted in enhanced immune responses upon T cell re-stimulation in vitro.Conclusion: These findings indicate that C1498-derived EVs have immunomodulatory effects on cell-mediated immune responses that could potentially be utilized to facilitate anti-leukemia immune responses.Keywords: extracellular vesicles, acute myeloid leukemia, immune responses
