CXCR2

CXCR2 is a G protein-coupled chemokine receptor that predominantly regulates neutrophil recruitment, leukocyte trafficking, and inflammatory responses through binding multiple ELR+ CXC chemokines, including CXCL1 and CXCL8/IL-8[1][2]. Mechanistically, CXCR2 activation triggers chemokine-dependent signaling pathways that promote integrin activation, cell migration, adhesion, and tissue infiltration, thereby coordinating innate immune responses during infection and tissue injury[1]. Beyond physiological inflammation, the CXCL-CXCR2 signaling axis contributes to angiogenesis, tumor cell migration, invasion, and stromal remodeling in multiple cancer types, including pancreatic, colorectal, breast, lung, and ovarian cancers[3][4][5]. In disease models, elevated CXCR2 signaling promotes recruitment of neutrophils and myeloid-derived suppressor cells, supporting tumor progression and immunosuppressive microenvironments[3][4]. Compared with the related receptor CXCR1, which shares CXCL8 responsiveness, CXCR2 exhibits broader ligand recognition and mediates diverse inflammatory and tumor-associated chemokine networks across immune, endothelial, epithelial, and stromal cells[2][5]. Therefore, CXCR2 has emerged as a major experimental and therapeutic target, and multiple CXCR2 antagonists have demonstrated activity in preclinical cancer, cardiovascular, lung injury, and inflammatory disease models by reducing leukocyte recruitment, angiogenesis, and pathological inflammation[1][2][3].