FABP4 Couples Lipid Metabolism to PD-L1 Stabilization in Immunosuppressive Macrophages

CD16⁺ monocyte population exhibits elevated FABP4-PD-L1 signaling and correlates with obesity and invasive breast cancer. These findings establish PD-L1 as a metabolically regulated protein and reveal a mechanism by which lipid excess drives immune evasion, suggesting that targeting FABP4 may enhance responses to immune checkpoint blockade. Highlights: FABP4 defines a lipid-responsive, immunosuppressive monocyte/macrophage subsetFABP4 links lipid sensing to PD-L1 expression in macrophagesFABP4 enables palmitic acid-dependent PD-L1 palmitoylation and stabilizationFABP4-PD-L1 signaling correlates with obesity and invasive breast cancer in humans.