Effect of HDAC Inhibitor Chidamide on PD-L1 Expression in Peripheral T-Cell Lymphoma.
10.19746/j.cnki.issn.1009-2137.2022.06.017
- Author:
Miao-Ming YAN
1
;
Zhao-Xuan LI
2
;
Chong CHEN
2
;
Wei ZHANG
1
;
Dao-Bin ZHOU
3
Author Information
1. Department of Hematology, Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
2. Department of Immunology, Institute of Basic Medical Science CAMS, School of Basic Medicine PUMC, Beijing 100005, China.
3. Department of Hematology, Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. E-mail: zhoudb@pumch.cn.
- Publication Type:Journal Article
- Keywords:
PD-1/PD-L1;
chidamide
- MeSH:
Humans;
Lymphoma, T-Cell, Peripheral;
Histone Deacetylase Inhibitors;
B7-H1 Antigen;
Janus Kinases;
Programmed Cell Death 1 Receptor;
Signal Transduction;
STAT Transcription Factors
- From:
Journal of Experimental Hematology
2022;30(6):1741-1745
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the role of chidamide in the regulatory mechanism of PD-1/PD-L1 immune escape signaling pathway in peripheral T-cell lymphoma.
METHODS:Jurkat cell line was treated with different concentrations of chidamide. The changes of PD-L1 and JAK/STAT pathway gene mRNA expression and PD-L1 protein expression on cell surface were detected by fluorescence quantitative PCR and flow cytometry after treatment.
RESULTS:Chidamide upregulated PD-L1 mRNA expression in Jurkat cell line in a dose-dependent manner (r=0.989). The mRNA expression of PD-L1 in 5.0 μmol/L group was 15.4 times higher than that in the control group. The proportion of PD-L1 positive cells in Jurkat cell line was less than 0.5%. Chidamide upregulated PD-L1 protein expression on Jurkat cell surface. Chidamide upregulated the mRNA expression of JAK2, STAT1 and STAT3 in Jurkat cell line. The level of up-regulation was obvious in high concentration group (5.0 μmol/L group). Meanwhile, the mRNA expression of SOCS1 and SOCS3, the negative regulatory genes upstream of the JAK/STA T pathway, were up-regulated.
CONCLUSION:In peripheral T-cell lymphoma, chidamide may up-regulate the expression of cell surface PD-L1 and induce T-cell chemokines by upregulation of STAT1 expression, thus improving the reaction rate of PD-1 monoclonal antibody and T-cell toxicity.
