STK11 coordinates IL-4 signaling with metabolic reprogramming to control M2 macrophage polarization and antitumor immunity.

ABSTRACT: Macrophages integrate microenvironmental cues to orchestrate complex transcriptional and metabolic programs that drive functional polarization. Here, we demonstrate that STK11 links interleukin-4 (IL-4) signaling with metabolic reprogramming to restrain alternatively activated (M2) macrophage polarization. Through integrative transcriptomic and metabolomic analyses, we identified STK11 as a key transcriptional and metabolic regulator during M2 polarization. STK11 deficiency enhanced the expression of M2-associated markers and promoted glutamine metabolism in IL-4-stimulated macrophages. Mechanistically, STK11 deficiency led to increased FOXO1 activation, thereby promoting M2 polarization. Pharmacological inhibition of FOXO1 or glutamine metabolism effectively reversed the enhanced M2 polar

SUBMITTER: Yang J 

PROVIDER: S-EPMC12466853 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature