CXCR2 is a G protein-coupled chemokine receptor primarily expressed on neutrophils and other immune cells that mediates chemotaxis and inflammation. The receptor binds IL-8 and related ligands (CXCL1, CXCL3, CXCL5) with high affinity, activating phosphatidylinositol-calcium signaling to trigger neutrophil migration and activation 12. Beyond acute inflammation, CXCR2 signaling reinforces cellular senescence through a p53-dependent, self-amplifying feedback loop where senescent cells secrete CXCR2-binding chemokines that sustain growth arrest 3. CXCR2 dysfunction contributes to multiple pathologies. In aortic dissection, the CXCL3/CXCR2 axis orchestrates neutrophil extracellular trap formation, promoting disease progression; blocking this axis ameliorates aortic rupture 4. In lung cancer, CXCR2 overexpression promotes tumor progression and chemoresistance, while CXCR2 inhibition enhances cisplatin efficacy by reducing immunosuppressive tumor-associated neutrophils 5. H. pylori infection upregulates CXCR2 expression and activates CXCR2-mediated cellular senescence, driving atrophic gastritis progression; pharmaceutical CXCR2 inhibition attenuates these effects 6. Additionally, CXCR2 expressed on nociceptive neurons mediates pain and inflammation in gouty arthritis through CXCL5-induced TRPA1 activation 7. In pancreatic cancer, CXCR2+ neutrophils and CAF-expressed CXCR2 promote metastasis and therapeutic resistance 89.