首页|下调USP37抑制PD-L1表达增强三阴性乳腺癌细胞免疫反应

下调USP37抑制PD-L1表达增强三阴性乳腺癌细胞免疫反应

Reducing USP37 enhances immune responses by inhibiting PD-L1 expression in triple-negative breast cancer cells MDA-MB-231

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目的:探讨下调USP37 表达对三阴性乳腺癌(TNBC)细胞程序性死亡受体配体1(PD-L1)表达量的影响及对其抗肿瘤免疫反应的作用.方法:应用免疫组织化学染色法检测TNBC组织中USP37 的表达量及其与PD-L1 表达量之间的相关性.反用siRNA瞬时转染技术降低人 TNBC细胞系MDA-MB-231 细胞中USP37 的表达.采用实时定量聚合酶链反应(qRT-PCR)、蛋白质印迹法(Western Blot)检测瞬时转染后MDA-MB-231 细胞中USP37 和PD-L1 的mRNA及蛋白质的表达水平.将瞬时转染后的MDA-MB-231 细胞与外周血单个核细胞(PBMC)进行共培养,采用CCK8 法评估PBMC对MDA-MB-231 细胞的杀伤作用,流式细胞术检测MDA-MB-231 细胞中PD-L1 的表达变化.结果:免疫组化结果显示,TNBC中USP37 高表达且与PD-L1 的表达量呈正相关(P<0.01).与转染对照组相比,下调USP37 后MDA-MB-231 细胞中USP37 和PD-L1 的mRNA、蛋白质表达量均显著降低.CCK8 实验显示,下调USP37 增强PBMC对MDA-MB-231 细胞的杀伤能力(P<0.01);流式细胞术显示,下调USP37 MDA-MB-231 细胞表面PD-L1 表达量下调(P<0.01).结论:下调USP37 可抑制MDA-MB-231 细胞PD-L1 的表达,影响TNBC的抗肿瘤免疫反应.
Objective:To investigate the effect of downregulating USP37 expression on programmed death-ligand 1(PD-L1)expression in triple-negative breast cancer(TNBC)cells and its role in tumor immune response.Methods:Immunohistochemistry was used to detect the expression of USP37 and its correlation with PD-L1 expression in TNBC tissues.siRNA-mediated transient transfection was performed to downregulate USP37 expression in MDA-MB-231 cells.qRT-PCR and Western Blot were used to measure the mRNA and protein levels of USP37 and PD-L1 in MDA-MB-231 cells after transient transfection.MDA-MB-231 cells transfected with siRNA were co-cultured with peripheral blood mononuclear cells(PBMCs),and CCK8 assay was used to evaluate the cytotoxic effect of PBMCs on MDA-MB-231 cells.Flow cytometry was used to detect changes in PD-L1 expression on MDA-MB-231 cells.Results:Immunohistochemistry showed that USP37 was highly expressed in TNBC tissues and positively correlated with PD-L1 expression(P<0.01).Compared to the control group,downregulation of USP37 significantly reduced the mRNA and protein levels of both USP37 and PD-L1 in MDA-MB-231 cells.CCK8 assay indicated that downregulation of USP37 enhanced PBMC-mediated cytotoxicity against MDA-MB-231 cells(P<0.01).Flow cytometry showed that the expression of PD-L1 on the surface of MDA-MB-231 cells was significantly reduced in the USP37 downregulation group(P<0.01).Conclusion:Downregulation of USP37 inhibits PD-L1 expression on MDA-MB-231 cells and influences the anti-tumor immune response in TNBC.

triple-negative breast cancerUSP37programmed death-ligand 1anti-tumor immune response

杨慧媛、徐世圣、秦涛、王海宁、周宓

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青岛大学附属青岛市市立医院/青岛市市立医院 肿瘤科,山东 青岛 266071

中国人民解放军海军第九七一医院 肿瘤科,山东 青岛 266071

三阴性乳腺癌 USP37 程序性死亡受体配体1 抗肿瘤免疫反应

2024

现代医学
东南大学

现代医学

CSTPCD
影响因子:0.703
ISSN:1671-7562
年,卷(期):2024.52(12)