Fig. 4
From: Functional polarization of tumor-associated macrophages dictated by metabolic reprogramming
Schematics of CD40 signaling-induced metabolic rewiring to support anti-tumorigenic functions of macrophages. CD40 activation engages glucose-independent metabolic pathways to induce epigenetic activation of pro-inflammatory M1 genes. CD40 signaling triggers FAO and glutamine metabolism to drive the TCA cycle. The citrate is shunted towards ACLY-dependent acetyl-CoA production to promote histone acetylation and M1 gene activation. Glutamine usage reinforces FAO-dependent anti-tumorigenic functions by maintaining the NAD + /NADH ratio via lactate pathway. Abbreviations: ACLY, ATP-citrate lyase; ATP, Adenosine triphosphate; Cpt1a, carnitine palmitoyltransferase 1A; FA, fatty acid; GLS, glutaminase; LDHA, lactate dehydrogenase A; ME1, malic enzyme 1; MDH1, malate dehydrogenase 1; OAA, Oxaloacetic acid; TCA: tricarboxylic acid (Created with BioRender.com)