CXCR2

C-X-C chemokine receptor type 2 (CXCR2, IL-8RB, CD128b) is a broadly reactive Gαi-coupled chemokine receptor for essentially all ELR-motif CXC chemokines, including CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7 and dimeric CXCL8. CXCR2 is the dominant chemokine receptor on neutrophils, where it integrates gradients of multiple chemokines to drive directional migration, and is also expressed on monocytes, mast cells, endothelial cells and neurons. The CXCR2 axis executes neutrophil recruitment in acute bacterial infection, reperfusion injury and COPD, where CXCL1/CXCL5-driven neutrophilia damages lung tissue. In oncology, CXCR2 has a prominent dual role: tumor- and stromal-cell-derived ELR+ chemokines attract neutrophils that become tumor-associated neutrophils or myeloid-derived suppressor cells, fostering angiogenesis, immune suppression and pre-metastatic niche formation; simultaneously, endothelial CXCR2 supports tumor angiogenesis. Small-molecule CXCR2 antagonists such as navixinert (AZD5069) and danirixin have been clinically evaluated for COPD, asthma and pancreatic cancer combination therapy.