C-X-C motif chemokine ligand 8 (CXCL8) (CXCL8)

C-X-C motif chemokine ligand 8 (CXCL8), commonly known as Interleukin-8 (IL-8), is a potent chemoattractant and pro-inflammatory cytokine primarily responsible for the recruitment of neutrophils and other immune cells to sites of inflammation (UniProt: P10145). In many solid tumors, high levels of CXCL8 are secreted by malignant cells and associated stroma, which typically correlates with poor prognosis, increased angiogenesis, and immune evasion (PubMed: 31515462). The therapeutic strategy involving engineered CXCR2 on autologous tumor-infiltrating lymphocytes (TILs) aims to exploit this CXCL8 gradient to improve the trafficking and infiltration of T-cells into the tumor mass (PubMed: 22547406). By overexpressing CXCR2—the high-affinity receptor for CXCL8—on the surface of TILs, these therapeutic cells can more effectively navigate the immunosuppressive tumor microenvironment and reach the core of the tumor (ClinicalTrials.gov: NCT01740557). This approach addresses a major limitation of conventional TIL therapy, which often fails due to poor homing and physical exclusion of T-cells from the tumor site. Clinical and preclinical studies are exploring this modification to enhance the efficacy of adoptive cell transfer in various solid malignancies, such as melanoma and renal cell carcinoma (Nature Communications: 13:2601).

Other names

Interleukin-8IL-8Neutrophil-activating factorNAFGranulocyte chemotactic protein 1GCP-1Monocyte-derived neutrophil chemotactic factor

Enhanced chemotactic recruitment of engineered autologous T-cells to the tumor microenvironment via the CXCL8-CXCR2 signaling axis.