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.
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.