Murine Leukemia-Derived Extracellular Vesicles Elicit Antitumor Immune Response

J Blood Med. 2021 May 17:12:277-285. doi: 10.2147/JBM.S308861. eCollection 2021.

Abstract

Background: 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: acute myeloid leukemia; extracellular vesicles; immune responses.

Grants and funding

These studies were supported by 5P30GM110759-04 and by funds provided by the Division of Hematology/Oncology, Rhode Island Hospital.