Asiaticoside modulates human NK cell functional fate by mediating metabolic flexibility in the tumor microenvironment

The study concludes that asiaticoside has significant potential as a strategy for "priming" NK cells in cellular immunotherapy. By demonstrating that asiaticoside degrades the TGF-β receptor, leading to reduced phosphorylation of SMAD2 and preventing its mitochondrial translocation, thereby maintaining mitochondrial integrity. Meantime, asiaticoside counteracts TGF-β-induced suppression of mitochondrial oxidative and aerobic respiration through the mTOR/DRP1 pathways. The research uncovers a previously unreported pathway for preserving mitochondrial respiration and NK cell functionality. A detailed mechanistic insight into how asiaticoside functions at the molecular level was explored. Its ability to counteract the immunosuppressive effects of TGF-β makes it a valuable candidate for enhancing the effectiveness of immunotherapies in treating a variety of tumors with elevated TGF-β levels.