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[Effect of HDAC Inhibitor Chidamide on PD-L1 Expression in Peripheral T-Cell Lymphoma]
Miao-Ming Yan1, Zhao-Xuan Li2, Chong Chen2
1Department of Hematology, Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
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.
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