The Phospholipid Bis(monoacylglycero)Phosphate Confers Antitumour Immunogenicity to Exosomes Secreted by Dendrogenin A, Which Activates Its Biosynthesis in Tumour Cells

Dendrogenin A (DDA) is a cholesterol-derived antitumour metabolite that promotes the secretion of immunogenic antitumour exosomes (DDA-sEV) enriched in bis(monoacylglycero)phosphate (BMP). BMP is a phospholipid specific to late endosomes and lysosomes, where it plays a crucial role in lipid degradation, regulates the fate of endosomal cholesterol, and contributes to intraluminal vesicle formation. Dysregulation of BMP biosynthesis is associated with multiple diseases. Here, we show that the DDA/LXRβ complex activates the transcription and activity of phospholipase D (PLD) and CLN5, two enzymes involved in BMP biosynthesis. Inhibition of PLD in DDA-treated tumour cells reduces BMP levels in DDA-sEV, impairs…

• IN
  Institut National de la Santé et de la Recherche Médicale
• LC
  Ligue Contre le Cancer
• UD
  Université de Toulouse
• CN
  Centre National de la Recherche Scientifique
• IN
  Institut National Du Cancer

  Award: PLBio 20‐160