Effects of Dasatinib on the Maturation of Monocyte-Derived Dendritic Cells Derived from Healthy Donors and Chronic Myelogenous Leukemia Patients.
10.19746/j.cnki.issn.1009-2137.2022.03.004
- Author:
Wan-Jun CAO
1
;
Jing-Ying DAI
2
;
Wen-Juan DONG
2
;
Xi WANG
2
;
Xiao-Dong WANG
2
;
Jing-Yi XIA
2
;
Xiao-Hua LI
2
;
Hua ZHOU
2
;
Jie CHEN
3
;
Lin HE
4
Author Information
1. 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.
2. 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.
3. 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,E-mail: Georgechen811019@126.com.
4. 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,E-mail: helin514@126.com.
- Publication Type:Journal Article
- Keywords:
dasatinib;
dendritic cell adjuvant;
dentritic cells;
immunomodulatory effect
- MeSH:
Cell Differentiation;
Cells, Cultured;
Dasatinib/pharmacology*;
Dendritic Cells;
HLA-DR Antigens/pharmacology*;
Humans;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism*;
Leukocytes, Mononuclear;
Monocytes
- From:
Journal of Experimental Hematology
2022;30(3):677-687
- CountryChina
- Language:Chinese
-
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 CD80+CD86+ 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 CD80+CD86+ 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.
