Mechanistically, we showed that transcriptional factor Bcl6 co-opted the demethylase Tet2 and the deacetylase SIRT1 to confer the epigenetic imprinting and mitochondrial metabolic traits to SMMs, bolstering the stability and longevity of trained immunity in tumor-associated macrophages (TAMs). This evidence concerns the gene BCL6 and neoplasm.