文献类型：期刊文献

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

作者：Lei, Jin[1];Cao, Xue-Wei[2,3];Li, Peng-Fei[1];Zhao, Jian[1,2];Wang, Fu-Jun[2,3,4]

机构：[1]East China Univ Sci & Technol, Dept Appl Biol, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, ECUST FONOW Joint Res Ctr Innovat Med, Shanghai, Peoples R China;[3]Zhejiang Fonow Med Co Ltd, New Drug R&D Ctr, Dongyang, Peoples R China;[4]Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, 1200 Cailun Rd, Shanghai 201203, Peoples R China

年份：2024

卷号：598

期号：24

起止页码：3053

外文期刊名：FEBS LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001337489800001)】；

基金：This work was supported by the National Natural Science Foundation of China (Grant No. 81571795 and 82104099) and also by Zhejiang Fonow Medicine Co., Ltd. (Grant No. F100-42106L).

语种：英文

外文关键词：cancer therapy; cholesterol; immunotherapy; MHC; PD-L1; platycodin D

摘要：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 beta (LXR-beta) as a potential PD target. Further studies showed that PD reduces PD-L1 levels by binding to LXR-beta and inhibiting LXR-beta 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.