文章：

SAHA介导的组蛋白去乙酰化酶抑制对肺癌细胞PD-L1表达的调控作用

Regulation of PD-L1 Expression by SAHA-Mediated Histone Deacetylase Inhibition in Lung Cancer Cells

原文发布日期：5 September 2025

DOI: 10.3390/cancers17172919

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: The effects of PD-L1 are mediated via its binding to the PD-1 receptor, which mediates the signals intracellularly to suppress T-cell responses. The expression levels of PD-L1 on cancer cells are an important indicator of immunosuppression and cause poor prognosis in several types of cancers. Therefore, the identification and characterization of mechanisms that regulate the expression of PD-L1 in cancer patients is very critical. Method: Our experiment was designed to determine the impact of histone deacetylase (HDAC) inhibitor on PD-L1 expression to reverse tumor-induced immunosuppression using H460 and HCC827 lung cancer cell lines. These cells were treated with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). PD-L1 expression levels were assessed along with key regulatory proteins, including p53, p21, acetyl-histones, DNMT3B, MGMT, and trimethyl histones. Results: In our experiments, suberoylanilide hydroxamic acid (SAHA) was able to reduce the expression of PD-L1 by 60% in a dose-dependent manner. While the level of PD-L1 was significantly reduced, a concurrent increase in levels of p53, p21, and acetyl histone levels were observed in H460 and HCC827 cells following SAHA treatment. Furthermore, SAHA treatment was able to decrease the levels of DNMT3B, MGMT, and tri-methyl histones. It appears that the decrease in PD-L1 expression observed is solely because of p53 or p21WAF1/CIP1-mediated negative control on the transcription process. Conclusion: Our results suggest that SAHA can be used along with immune checkpoint inhibitors to potentiate the therapeutic outcomes in patients with excessive immunosuppression due to PD-L1 expression.

摘要翻译： 

背景/目的：PD-L1的作用通过其与PD-1受体结合介导，该受体在细胞内传递信号以抑制T细胞应答。癌细胞上PD-L1的表达水平是免疫抑制的重要指标，并在多种癌症中导致不良预后。因此，识别并阐明调控癌症患者PD-L1表达的机制至关重要。方法：本研究旨在通过H460和HCC827肺癌细胞系，探究组蛋白去乙酰化酶（HDAC）抑制剂对PD-L1表达的影响，以逆转肿瘤诱导的免疫抑制。实验采用HDAC抑制剂辛二酰苯胺异羟肟酸（SAHA）处理细胞，评估PD-L1表达水平及关键调控蛋白（包括p53、p21、乙酰化组蛋白、DNMT3B、MGMT和三甲基化组蛋白）的变化。结果：实验显示，SAHA能以剂量依赖方式使PD-L1表达降低60%。在H460和HCC827细胞中，SAHA处理显著降低PD-L1水平的同时，伴随p53、p21及乙酰化组蛋白水平的升高。此外，SAHA还能降低DNMT3B、MGMT和三甲基化组蛋白水平。观察到的PD-L1表达下降似乎完全由p53或p21WAF1/CIP1介导的转录过程负调控所致。结论：本研究结果表明，SAHA可与免疫检查点抑制剂联用，增强因PD-L1表达导致过度免疫抑制患者的治疗效果。

原文链接：

Regulation of PD-L1 Expression by SAHA-Mediated Histone Deacetylase Inhibition in Lung Cancer Cells