Yan Miao-Ming, Li Zhao-Xuan, Chen Chong, Zhang Wei, Zhou Dao-Bin
Department of Hematology, Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Department of Immunology, Institute of Basic Medical Science CAMS, School of Basic Medicine PUMC, Beijing 100005, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Dec;30(6):1741-1745. doi: 10.19746/j.cnki.issn.1009-2137.2022.06.017.
To explore the role of chidamide in the regulatory mechanism of PD-1/PD-L1 immune escape signaling pathway in peripheral T-cell lymphoma.
Jurkat cell line was treated with different concentrations of chidamide. The changes of PD-L1 and pathway gene mRNA expression and PD-L1 protein expression on cell surface were detected by fluorescence quantitative PCR and flow cytometry after treatment.
Chidamide upregulated mRNA expression in Jurkat cell line in a dose-dependent manner (=0.989). The mRNA expression of 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 and 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 and , the negative regulatory genes upstream of the T pathway, were up-regulated.
In peripheral T-cell lymphoma, chidamide may up-regulate the expression of cell surface PD-L1 and induce T-cell chemokines by upregulation of expression, thus improving the reaction rate of PD-1 monoclonal antibody and T-cell toxicity.
探讨西达本胺在外周T细胞淋巴瘤PD-1/PD-L1免疫逃逸信号通路调控机制中的作用。
用不同浓度的西达本胺处理Jurkat细胞系。处理后，通过荧光定量PCR和流式细胞术检测PD-L1及相关通路基因mRNA表达的变化以及细胞表面PD-L1蛋白表达情况。
西达本胺以剂量依赖方式上调Jurkat细胞系中相关mRNA表达（r = 0.989）。5.0 μmol/L组中相关mRNA表达是对照组的15.4倍。Jurkat细胞系中PD-L1阳性细胞比例小于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细胞系中相关基因及另一基因的mRNA表达。高浓度组（5.0 μmol/L组）上调水平明显。同时，T细胞通路上游的负调控基因的mRNA表达上调。
在外周T细胞淋巴瘤中，西达本胺可能上调细胞表面PD-L1表达，并通过上调相关基因表达诱导T细胞趋化因子，从而提高PD-1单克隆抗体反应率及T细胞毒性。
