过表达 miR-195 通过靶向 PD-L1 减弱弥漫性大 B 细胞淋巴瘤的免疫逃逸。
Overexpressed miR-195 attenuated immune escape of diffuse large B-cell lymphoma by targeting PD-L1.
机构信息
Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People'S Hospital of Changzhou, Changzhou, 213003, Jiangsu, China.
Department of Oncology, The Third Affiliated Hospital of Suzhou University, The First People'S Hospital of Changzhou, No. 185 Juqian Street, Changzhou, 213003, Jiangsu, China.
出版信息
Biomed Pharmacother. 2018 Feb;98:95-101. doi: 10.1016/j.biopha.2017.11.146. Epub 2017 Dec 13.
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) seriously threatens patients life with the morbidity increases at a high rate. Immune response disorder is the potential factor that induces DLBCL, while the potential mechanism still not fully understand.
METHODS
Real-time PCR and western blot were performed to determine genes expression. Flow cytometry was employed to detect the expression of PD-1 and the ratio of PD-1T cells. Enzyme-linked immune sorbent assay (ELISA) was used to determine the cytokines secretion.
RESULTS
MiR-195 was down-regulated, while PD-L1 was up-regulated in DLBCL tissues, and the rate of PD-1T cells was increased in T cells of peripheral blood in DLBCL. Overexpressed miR-195 suppressed the expression of PD-L1. Moreover, miR-195 overexpression significantly promoted the secretion of IFN-γ and TNF-α, but decreased IL-10 and PD-1T cells rate in the co-culture model of T cells and OCI-Ly-10 cells. MiR-195 targets PD-L1 to regulate the expression of IFN-γ, TNF-α, IL-10 and the rate of PD-1T cells.
CONCLUSION
MiR-195 regulated immune response of DLBCL through targeting PD-L1.
背景
弥漫性大 B 细胞淋巴瘤（DLBCL）的发病率呈高速增长态势，严重威胁患者生命。免疫应答紊乱是诱发 DLBCL 的潜在因素，但其潜在机制尚不完全清楚。
方法
采用实时 PCR 和 Western blot 检测基因表达，流式细胞术检测 PD-1 及 PD-1T 细胞的比例，酶联免疫吸附试验（ELISA）检测细胞因子分泌。
结果
在 DLBCL 组织中 miR-195 呈低表达，而 PD-L1 呈高表达，DLBCL 患者外周血 T 细胞中 PD-1T 细胞比例升高。过表达 miR-195 可抑制 PD-L1 的表达。此外，在 T 细胞与 OCI-Ly-10 细胞共培养模型中，miR-195 过表达可显著促进 IFN-γ 和 TNF-α 的分泌，降低 IL-10 和 PD-1T 细胞的比例。miR-195 通过靶向 PD-L1 调节 IFN-γ、TNF-α、IL-10 和 PD-1T 细胞的表达。
结论
miR-195 通过靶向 PD-L1 调节 DLBCL 的免疫应答。
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