Yao Ye, Wang Chun, Wei Wei, Shen Chang, Deng Xiaohui, Chen Linjun, Ma Liyuan, Hao Siguo
Department of Hematology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Hematology, The First People's Hospital of Shanghai Affiliated to Shanghai Jiaotong University, Shanghai, China.
PLoS One. 2014 Mar 12;9(3):e91463. doi: 10.1371/journal.pone.0091463. eCollection 2014.
Dendritic cells (DCs) and tumor cell-derived exosomes have been used to develop antitumor vaccines. However, the biological properties and antileukemic effects of leukemia cell-derived exosomes (LEXs) are not well described. In this study, the biological properties and induction of antileukemic immunity of LEXs were investigated using transmission electron microscopy, western blot analysis, cytotoxicity assays, and animal studies. Similar to other tumor cells, leukemia cells release exosomes. Exosomes derived from K562 leukemia cells (LEXK562) are membrane-bound vesicles with diameters of approximately 50-100 μm and harbor adhesion molecules (e.g., intercellular adhesion molecule-1) and immunologically associated molecules (e.g., heat shock protein 70). In cytotoxicity assays and animal studies, LEXs-pulsed DCs induced an antileukemic cytotoxic T-lymphocyte immune response and antileukemic immunity more effectively than did LEXs and non-pulsed DCs (P<0.05). Therefore, LEXs may harbor antigens and immunological molecules associated with leukemia cells. As such, LEX-based vaccines may be a promising strategy for prolonging disease-free survival in patients with leukemia after chemotherapy or hematopoietic stem cell transplantation.
树突状细胞（DCs）和肿瘤细胞衍生的外泌体已被用于开发抗肿瘤疫苗。然而，白血病细胞衍生的外泌体（LEXs）的生物学特性和抗白血病作用尚未得到充分描述。在本研究中，使用透射电子显微镜、蛋白质印迹分析、细胞毒性测定和动物研究来研究LEXs的生物学特性和抗白血病免疫的诱导。与其他肿瘤细胞类似，白血病细胞会释放外泌体。源自K562白血病细胞的外泌体（LEXK562）是直径约为50 - 100μm的膜结合囊泡，含有粘附分子（如细胞间粘附分子-1）和免疫相关分子（如热休克蛋白70）。在细胞毒性测定和动物研究中，LEXs脉冲的DCs比LEXs和未脉冲的DCs更有效地诱导抗白血病细胞毒性T淋巴细胞免疫反应和抗白血病免疫（P<0.05）。因此，LEXs可能含有与白血病细胞相关的抗原和免疫分子。因此，基于LEXs的疫苗可能是延长白血病患者化疗或造血干细胞移植后无病生存期的一种有前景的策略。
