C-X-C chemokine receptor type 2 (CXCR2) (CXCR2)

C-X-C chemokine receptor type 2 (CXCR2) is a G protein-coupled receptor primarily expressed on neutrophils and other myeloid cells, where it mediates chemotaxis in response to ELR-positive (ELR+) CXC chemokines such as CXCL1 through CXCL8 (IL-8) (UniProt: P25025). In many solid tumors, these chemokines are overexpressed to promote angiogenesis and recruit immunosuppressive cells, creating a gradient that can be exploited for therapeutic homing (PubMed: 25223445). By genetically engineering autologous tumor-infiltrating lymphocytes (TILs) to express CXCR2, researchers aim to enhance the ability of these T cells to penetrate the often-impenetrable tumor microenvironment (PubMed: 31043417). This gain-of-function approach, exemplified by clinical candidates like IOV-3001, is designed to turn the tumor's own signaling molecules into a beacon for the immune system, potentially improving outcomes in cold tumors like melanoma and non-small cell lung cancer (Iovance Biotherapeutics). While CXCR2 is also a target for small-molecule antagonists to reduce inflammation, its role in engineered TILs is to serve as a critical sensor for improved therapeutic delivery and efficacy.

Other names

Interleukin 8 receptor betaIL8RBCD182CXC-R2CDw128bELR-positive CXC chemokine receptor

Genetic engineering of autologous tumor-infiltrating lymphocytes (TILs) to overexpress the CXCR2 receptor, enabling these cells to sense and migrate along the concentration gradient of ELR-positive (ELR+) CXC chemokines, such as CXCL8 (IL-8), which are secreted by tumor and stromal cells to facilitate T-cell infiltration into the tumor microenvironment (PubMed: 31043417).