Attenuated A20 expression of acute myeloid leukemia-derived dendritic cells increased the anti-leukemia immune response of autologous cytolytic T cells

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• 作者：Xiaoying Zhang^a ; ^b ; ¹ ; Yongfeng Su^a ; ^b ; ¹ ; Haifeng Song^a ; ^b ; Zhiyong Yu^a ; ^b ; Bin Zhang^a ; ^b ; ^{zb307ctc@163.com" class="auth_mail} ; Hu Chen^a ; ^b ; ^{chenhu217@aliyun.com" class="auth_mail}
• 关键词：Minimal residual disease (MRD) ; Acute myeloid leukemia (AML) ; Zinc finger protein A20 ; AML-derived DCs (AML-DCs)
• 刊名：Leukemia Research
• 出版年：June 2014
• 年：2014
• 卷：38
• 期：6
• 页码：673-681
• 全文大小：2054 K

文摘

Previous studies reported leukemic cells from acute myeloid leukemia (AML) patients can differentiate into dendritic cells (DCs), which had some immunoregulatory dysfunctions to effectively stimulate autologous CTLs’ anti-leukemia immune response. The zinc-finger protein A20, a negative regulator of the nuclear factor (NF)-魏B pathway, was found to play a crucial role in controlling the maturation and function of human monocyte-derived DCs. However, the effects of A20 in AML derived DCs (AML-DCs) have not yet been evaluated. In this study, A20 expression was up-regulated in AML-DCs activated with tumor necrosis factor (TNF)-伪. Then, A20 attenuation with siRNA in AML-DC enhanced the expression of several co-stimulatory molecules and proinflammatory cytokines. Furthermore, after A20 attenuation in AML-DCs, the autologous cytolytic T cells (CTLs) induced by AML-DCs had higher killing capability and specificity for primary AML cells. Additionally, receptor-interacting protein (RIP) and the NF-魏Bp65 pathway were elevated in AML-DCs when A20 was reduced. Hence, this study identified A20 as a negative regulator for controlling AML-DC maturation and immunostimulatory potency, as A20 down-regulation resulted in AML-DCs with enhanced autologous CTLs immune capacity through the NF-魏B pathway.