Interleukin-8 (CXCL8) (IL-8)

Interleukin-8 (IL-8), also known as CXCL8, is a pro-inflammatory chemokine that plays a critical role in the recruitment and activation of neutrophils (UniProt P10145). Beyond its immunological functions, IL-8 is a potent promoter of angiogenesis, stimulating the proliferation, migration, and survival of endothelial cells through its interaction with the G protein-coupled receptors CXCR1 and CXCR2 (PubMed: 25103502). In the context of oncology, many tumors overexpress IL-8 to facilitate neovascularization, promote epithelial-mesenchymal transition (EMT), and recruit myeloid-derived suppressor cells (MDSCs) to the tumor microenvironment (PubMed: 31110137). Therapeutic strategies targeting this signaling axis include monoclonal antibodies like BMS-986253 that neutralize the IL-8 ligand and small molecule antagonists of the CXCR1/2 receptors such as Reparixin (ClinicalTrials.gov). These interventions aim to inhibit tumor growth and metastasis by disrupting the angiogenic and immunosuppressive environment driven by IL-8. Elevated levels of IL-8 are also associated with resistance to various therapies, including immune checkpoint inhibitors and anti-VEGF agents (PubMed: 32398863). Consequently, targeting IL-8-driven signaling is an active area of research to improve outcomes in patients with advanced solid tumors.

Other names

CXCL8Interleukin-8Neutrophil-activating factorMonocyte-derived neutrophil chemotactic factorAMCF-IEmoctakinGCP-1NAP-1

Drugs targeting this pathway work by either neutralizing the Interleukin-8 ligand (e.g., BMS-986253) to prevent it from binding to its receptors, or by acting as competitive antagonists for the C-X-C motif chemokine receptors 1 and 2 (CXCR1/CXCR2) (PubMed: 28453464). This blockade inhibits the activation of downstream signaling pathways such as PI3K/Akt and MAPK, which are essential for endothelial cell survival and migration during angiogenesis (PubMed: 12644482). By disrupting these signals, these agents reduce tumor-associated neovascularization and decrease the infiltration of immunosuppressive myeloid cells into the tumor (PubMed: 29654270).