Pando Alejandro, Fast Loren, Dubielecka Patrycja M, Chorzalska Anna, Wen Sicheng, Reagan John
Division of Hematology/Oncology, Department of Medicine, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, Providence, RI, USA.
J Blood Med. 2021 May 17;12:277-285. doi: 10.2147/JBM.S308861. eCollection 2021.
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.
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.
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.
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.
细胞外囊泡（EVs）是细胞分泌的异质性脂质双层颗粒。EVs包含蛋白质、RNA、DNA及其他具有免疫调节作用的物质。癌症来源的EVs在体内具有免疫调节作用，具有免疫抑制和促进肿瘤生长的能力。然而，癌症来源的EVs也已被用于挖掘其抗癌潜力。
为评估急性髓系白血病（AML）细胞产生的EVs的免疫调节作用，我们分离了小鼠AML细胞系C1498分泌的囊泡，并研究了它们对体外和体内免疫反应的影响。
这些白血病来源的EVs在体外可诱导CD3+细胞增殖增加，并增强CD3+细胞对白血病细胞的细胞溶解活性。将白血病来源的EVs注射到同基因的未致敏小鼠体内可诱导体内T细胞反应，并在体外T细胞再次刺激时导致免疫反应增强。
这些发现表明，C1498来源的EVs对细胞介导的免疫反应具有免疫调节作用，这可能被用于促进抗白血病免疫反应。
