25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages
Cholesterol increases macrophage-mediated inflammation, but how oxysterols control tumor-associated macrophages (TAMs) remains unclear. Xiao et al. show that TAMs exhibit elevated expression of CH25H, resulting in lysosome-accumulated 25HC that activates AMPKα to promote STAT6-dependent ARG1 production. CH25H-deficient macrophages switch “cold tumors” into “hot tumors” and improve anti-PD-1-mediated anti-tumor efficacy.