Attenuated A20 expression of acute myeloid leukemia-derived dendritic cells increased the anti-leukemia immune response of autologous cytolytic T cells.
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)-κB 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)-α. 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-κBp65 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-κB pathway.
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China; Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China.
Xiaoying
X
Zhang
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China; Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China.
Yongfeng
Y
Su
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China; Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China.
Haifeng
H
Song
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China; Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China.
Zhiyong
Z
Yu
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China; Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China. Electronic address: zb307ctc@163.com.
Bin
B
Zhang
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China; Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China. Electronic address: chenhu217@aliyun.com.
Hu
H
Chen
D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology*; D016162:Genes, Wilms Tumor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D009687:Nuclear Proteins / Q000502:physiology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D016207:Cytokines; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D051996:Transcription Factor RelA; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
AML-derived DCs (AML-DCs); Acute myeloid leukemia (AML); Minimal residual disease (MRD); Zinc finger protein A20