Interleukin-8 (CXCL8) signaling axis (IL-8 axis)

The Interleukin-8 (IL-8) signaling axis, primarily composed of the chemokine CXCL8 and its two high-affinity G protein-coupled receptors, CXCR1 and CXCR2, is a critical mediator of the inflammatory response and tumor microenvironment dynamics. In healthy physiology, this axis governs the recruitment and activation of neutrophils to sites of infection or injury. However, in the context of oncology, the IL-8 axis is frequently hijacked to promote tumor progression through the induction of angiogenesis, the recruitment of myeloid-derived suppressor cells (MDSCs), and the enhancement of epithelial-to-mesenchymal transition (EMT). Therapeutic strategies targeting this axis include monoclonal antibodies designed to sequester circulating IL-8 and small molecule inhibitors that block receptor activity. By disrupting this signaling, researchers aim to reduce tumor-associated inflammation, overcome resistance to immune checkpoint inhibitors, and limit metastatic spread.

Other names

CXCL8-CXCR1/2 axisInterleukin-8 signaling pathwayCXCL8 signalingIL-8/CXCR1/CXCR2 axis

Monoclonal antibodies neutralize the IL-8 ligand to prevent receptor binding, while small molecule antagonists competitively inhibit the CXCR1 and CXCR2 receptors to block downstream signaling cascades.