Zhen Zijun, Yang Kaibin, Ye Litong, You Zhiyao, Chen Rirong, Liu Ying, He Youjian
State Key Laboratory of Oncology in South ChinaGuangzhou, China; Department of Pediatric Oncology, Sun Yat-sen University Cancer CenterGuangzhou, China; Collaborative Innovation Center of Cancer MedicineGuangzhou, China.
State Key Laboratory of Oncology in South ChinaGuangzhou, China; Sun Yat-sen University Zhongshan School of MedicineGuangzhou, China.
Am J Cancer Res. 2017 Feb 1;7(2):334-345. eCollection 2017.
Neuroblastoma stem cells (NSCs) can cause drug resistance and tumor recurrence. This study aimed to enhance the lytic effect of dendritic cells (DCs) co-cultured with cytokine-induced killer (CIK) cells. NSCs were obtained by suspension culture, and DC-CIK cells were loaded with extracted NSC membrane-based microparticles (MMPs) before evaluating the lytic effect of DC-CIK cells on NSCs. After inhibiting the function or expression of human leukocyte antigen-E (HLA-E) in NSCs by anti-HLA-E monoclonal antibody or siRNA, the DC-CIK cell lytic effect on NSCs was re-assessed. NSC nestin expression was high, but glial fibrillary acid protein expression and class IIIβ-tubulin-1 expression were low. Moreover, NSCs exhibited strong tumorigenic ability in nude mice. Loading DCs with NSC-derived MMPs induced the differentiation of DCs and CIK cells and enhanced the killing of NSCs by DC-CIK cells. Inhibiting the function or expression of HLA-E in NSCs further enhanced the cytolytic capability of DC-CIK cells loaded with NSC-derived MMPs. HLA-E inhibitor can enhance the killing of NSC by DC-CIK cells loaded with NSC-derived MMPs.
神经母细胞瘤干细胞（NSCs）可导致耐药性和肿瘤复发。本研究旨在增强与细胞因子诱导的杀伤细胞（CIK）共培养的树突状细胞（DCs）的裂解作用。通过悬浮培养获得NSCs，并在评估DC-CIK细胞对NSCs的裂解作用之前，用提取的基于NSC膜的微粒（MMPs）负载DC-CIK细胞。在用抗HLA-E单克隆抗体或siRNA抑制NSCs中人白细胞抗原-E（HLA-E）的功能或表达后，重新评估DC-CIK细胞对NSCs的裂解作用。NSC巢蛋白表达高，但胶质纤维酸性蛋白表达和IIIβ-微管蛋白-1表达低。此外，NSCs在裸鼠中表现出很强的致瘤能力。用NSC来源的MMPs负载DCs可诱导DCs和CIK细胞分化，并增强DC-CIK细胞对NSCs的杀伤作用。抑制NSCs中HLA-E的功能或表达可进一步增强负载NSC来源MMPs的DC-CIK细胞的溶细胞能力。HLA-E抑制剂可增强负载NSC来源MMPs的DC-CIK细胞对NSC的杀伤作用。
