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.
题目: HDAC抑制剂西达本胺对外周T细胞淋巴瘤PD-L1表达的影响.
目的: 探讨西达本胺对外周T细胞淋巴瘤PD-1/PD-L1免疫逃逸信号通路调控机制的作用。.
方法: 使用不同浓度梯度的西达本胺处理Jurkat细胞系，通过荧光定量PCR与流式细胞术检测西达本胺处理后Jurkat细胞系PD-L1和 JAK/STAT 通路基因mRNA表达及细胞表面PD-L1蛋白表达的变化。.
结果: 西达本胺上调Jurkat细胞系 PD-L1 的mRNA表达，上调水平呈剂量依赖（r=0.989），5.0 μmol/L组 PD-L1 的mRNA表达是无处理组的15.4倍。Jurkat细胞系PD-L1+细胞比例不足0.5%。西达本胺上调Jurkat细胞表面PD-L1蛋白表达。西达本胺上调Jurkat细胞系 JAK2、STAT1、STAT3 的mRNA表达，高浓度组（5.0 μmol/L组）上调水平明显。同时 JAK/STAT 通路上游负调控基因 SOCS1、SOCS3 的mRNA表达上调。.
结论: 外周T细胞淋巴瘤中，西达本胺可能通过上调 STAT1 上调细胞表面PD-L1，并诱导T细胞趋化因子，提高PD-1单抗的反应率及T细胞毒性作用。.
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