CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions

Abstract Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. Mechanistically, glutamine usage reinforces FAO-induced pro-inflammatory and anti-tumorigenic…

• CR
  Cancer Research Institute
• MR
  Melanoma Research Alliance
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Awards: IZLCZ0_206083, 31003A_182470
• FW
  Fonds Wetenschappelijk Onderzoek
• KL
  KU Leuven
• NH
  National Health Research Institutes
• UD
  Université de Lausanne
• FB
  Fonds Baillet Latour