CXCL16 is a C-X-C chemokine that functions as both a chemoattractant and scavenger receptor, with critical roles in immune cell recruitment and inflammatory responses. As a soluble ligand, CXCL16 binds specifically to its receptor CXCR6 on immune cells, mediating chemotaxis of CD8+ T cells, natural killer T (NKT) cells, and γδ T cells 123. CXCL16 expression is regulated by multiple signaling pathways including NF-κB and STAT3 activation in dendritic cells and keratinocytes 23, and by glycolytic reprogramming in myeloid cells 4. In cancer immunology, CXCL16-CXCR6 interactions mediate T cell infiltration into tumors and enhance immunotherapy efficacy 526. CXCL16 is upregulated during hepatocellular carcinoma angiogenesis through Piezo1-HIF-1α signaling 7. However, CXCL16 expression shows context-dependent pathologic roles: elevated CXCL16-CXCR6 signaling contributes to psoriatic inflammation 3 and maladaptive immune responses in spinal cord injury 4. In cognitive impairment, elevated cerebrospinal fluid CXCL16 promotes antigen-specific CD8+ T cell recruitment to the brain 8. These findings establish CXCL16 as a key immunoregulatory molecule whose expression and signaling axis represents both therapeutic targets and opportunities for enhancing anti-tumor immunity.