HLA-E inhibitor enhances the killing of neuroblastoma stem cells by co-cultured dendritic cells and cytokine-induced killer cells loaded with membrane-based microparticles.
American journal of cancer research(2017)
摘要
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.
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