CCL3 (C-C motif chemokine ligand 3) is a pleiotropic CC chemokine with context-dependent roles in immune regulation and disease pathogenesis. Primary function: CCL3 acts as a chemoattractant that binds CCR1, CCR4, and CCR5 receptors to recruit and activate immune cells, particularly macrophages and neutrophils 1. Mechanism: CCL3 promotes proinflammatory macrophage polarization via CCR5-p38/interferon regulatory factor 5 signaling 2 and enhances macrophage antigen presentation through increased lysosomal activity and MHC II upregulation 3. In neutrophils, CCL3 sustains survival in hypoxic tumor regions via CCR1-dependent signaling 4. Disease relevance: CCL3 exhibits dual roles in cancer—enhancing docetaxel chemosensitivity in breast cancer through macrophage-mediated tumor cell phagocytosis 2, yet promoting pro-tumor neutrophil differentiation in growing tumors 4. In silicosis, CCL3+ neutrophils promote lung fibrosis via HBEGF-CD44 and CSF1-CSF1R crosstalk with monocytes 5. In intervertebral disc degeneration, Hippo signaling activates CCL3 production by chondrocytes, recruiting osteoclasts 6. Clinical significance: CCL3 expression correlates with improved prognosis in breast cancer and HCC, predicting better immunotherapy response 23. Targeted CCL3 delivery enhances immune checkpoint blockade efficacy 3. KAT7 suppresses CCL3 in osteosarcoma, suggesting therapeutic potential 7.