Platycodin D reduces PD-L1 levels by inhibiting LXR-β activity and combines with nintedanib to enhance the tumor-killing effect of T cells.

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Jin Lei, Xue-Wei Cao, Peng-Fei Li, Jian Zhao, Fu-Jun Wang
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引用次数: 0

Abstract

Most tumors are resistant to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors, which may be due to impaired antigen presentation resulting from the downregulation of major histocompatibility complex class I (MHC-I) expression on tumor cells. We observed that platycodin D (PD), polygalacin D, and platycodin D2, which are plant-derived triterpenoid saponins, significantly reduced PD-L1 levels. RNA sequencing and the PharmMapper database analysis identified liver X receptor β (LXR-β) as a potential PD target. Further studies showed that PD reduces PD-L1 levels by binding to LXR-β and inhibiting LXR-β activity. Coadministration of PD and nintedanib, known to upregulate MHC-I expression, enhanced tumor recognition and killing by T cells. This study provides new insights into PD applications and mechanisms.

Platycodin D通过抑制LXR-β活性来降低PD-L1水平,并与nintedanib联用,增强T细胞的肿瘤杀伤效果。
大多数肿瘤对程序性细胞死亡蛋白1(PD-1)/程序性死亡配体1(PD-L1)检查点抑制剂具有抗药性,这可能是由于肿瘤细胞上主要组织相容性复合体I类(MHC-I)表达下调导致抗原递呈受损。我们观察到,桔梗皂苷 D (PD)、远志皂苷 D 和桔梗皂苷 D2 这些植物源三萜皂苷能够显著降低 PD-L1 水平。RNA 测序和 PharmMapper 数据库分析发现肝 X 受体 β(LXR-β)是 PD 的潜在靶点。进一步的研究表明,PD 可通过与 LXR-β 结合并抑制 LXR-β 的活性来降低 PD-L1 水平。PD与已知能上调MHC-I表达的宁替尼(nintedanib)联合用药可增强T细胞对肿瘤的识别和杀伤。这项研究为PD的应用和机制提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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