达沙替尼对来自健康供体和慢性粒细胞白血病患者的单核细胞衍生树突状细胞成熟的影响

[Effects of Dasatinib on the Maturation of Monocyte-Derived Dendritic Cells Derived from Healthy Donors and Chronic Myelogenous Leukemia Patients].

作者信息

Cao Wan-Jun, Dai Jing-Ying, Dong Wen-Juan, Wang Xi, Wang Xiao-Dong, Xia Jing-Yi, Li Xiao-Hua, Zhou Hua, Chen Jie, He Lin

机构信息

School of Pharmacy, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China,Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu 610000, Sichuan Province, China.

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu 610000, Sichuan Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Jun;30(3):677-687. doi: 10.19746/j.cnki.issn.1009-2137.2022.03.004.

DOI:10.19746/j.cnki.issn.1009-2137.2022.03.004

PMID:35680790

Abstract

OBJECTIVE

To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients.

METHODS

Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. The generation of moDCs from PBMCs was completed after 7 days of incubation in DC I culture medium, and another 3 days of incubation in DC II culture medium with or without 25 nmol/L dasatinib. On the 10th day, cells were harvested and expression of molecules of maturation related marker were assessed by flow cytometry. The CD80CD86 cell population in total cells was gated as DCs in the fluorescence-activated cell storting (FACS) analyzing system, then the expression of CD83, CD40 or HLA-DR in this population was analyzed respectively.

RESULTS

The proportion of CD80CD86 cells in total cells didn't show a statistical difference between HD group and patient group (89.46%±9.70% vs 87.39%±9.34%, P=0.690). Dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.008) and HLA-DR (P=0.028) on moDCs derived from HDs compared with the control group, while the expression of CD83 on moDCs didn't show a significant difference between dasatinib group and the control group (P=0.428). Meanwhile, dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.023), CD83 (P=0.038) and HLA-DR (P=0.001) on moDCs derived from patients compared with the control group.

CONCLUSION

For CML patients, the same high proportion of moDCs as HDs can be induced in vitro, which provides a basis for the application of DC-based immunotherapy strategy. Dasatinib at the concentration of 25 nmol/L can efficiently promote the maturation of moDCs derived from HDs and CML patients in vitro. Dasatinib shows potential as a DC adjuvant to be applied in DC-based immunotherapy strategies, such as DC vaccine and DC cell-therapy.

摘要

目的

研究达沙替尼对健康供者（HD）和慢性髓性白血病（CML）患者来源的单核细胞衍生树突状细胞（moDCs）成熟的影响。

方法

从经伊马替尼治疗达到MR4.5缓解的HD（n = 10）和CML患者（n = 10）中分离外周血单个核细胞（PBMCs）。PBMCs在DC I培养基中孵育7天后完成moDCs的生成，然后在含或不含25 nmol/L达沙替尼的DC II培养基中再孵育3天。在第10天收获细胞，通过流式细胞术评估成熟相关标志物分子的表达。在荧光激活细胞分选（FACS）分析系统中，将总细胞中的CD80CD86细胞群作为DCs进行门控，然后分别分析该群体中CD83、CD40或HLA - DR的表达。

结果

HD组和患者组总细胞中CD80CD86细胞的比例无统计学差异（89.46%±9.70%对87.39%±9.34%，P = 0.690）。与对照组相比，达沙替尼显著增强了HD来源的moDCs表面标志物CD40（P = 0.008）和HLA - DR（P = 0.028）的表达，而达沙替尼组和对照组之间moDCs上CD83的表达无显著差异（P = 0.428）。同时，与对照组相比，达沙替尼显著增强了患者来源的moDCs表面标志物CD40（P = 0.023）、CD83（P = 0.038）和HLA - DR（P = 0.001）的表达。