Liang et al. reveal that TREM2+ LAMs recycle fatty acids through efferocytosis to support tumor adaptation to immune-checkpoint blockade. The fatty acid-containing extracellular vesicles fuel acetyl-CoA-dependent H3K36 acetylation to activate MYC and TGF-β programs. Genetic or pharmacologic TREM2 inhibition restores therapeutic sensitivity through epigenetic remodeling of immunosuppressive tumor microenvironment.
