These findings suggested that DLBCL-derived exosomal ENO2 accelerated glycolysis via GSK3β/β-catenin/c-Myc signaling pathway to ultimately promote macrophages to an M2-like phenotype, which can promote the proliferation, migration and invasion of DLBCL, suggesting that exosomal ENO2 may be a promising therapeutic target and prognostic biomarker for DLBCL. This evidence concerns the gene GSK3B and diffuse large B-cell lymphoma.