Inducible T-cell costimulator ligand (ICOSL) (ICOSL)

Inducible T-cell costimulator ligand (ICOSL), also known as CD275 or B7-H2, is a transmembrane glycoprotein belonging to the B7 family of costimulatory molecules [UniProt: O75144]. It is primarily expressed on professional antigen-presenting cells, such as B cells, dendritic cells, and macrophages, and its expression can be induced on non-hematopoietic cells like endothelial cells and certain tumor cells [NCBI Gene: 23308]. ICOSL serves as the cognate ligand for the ICOS receptor (CD278) found on activated T cells. The ICOS-ICOSL interaction is essential for T-cell proliferation, the production of cytokines like IL-4 and IL-21, and the formation of germinal centers, which are critical for high-affinity antibody production and B-cell memory [PMID: 11169416]. In clinical contexts, dysregulation of the ICOSL pathway is strongly linked to the pathogenesis of autoimmune diseases, particularly systemic lupus erythematosus (SLE) and rheumatoid arthritis, where it drives the production of pathogenic autoantibodies [PMID: 28847458]. In oncology, ICOSL expression within the tumor microenvironment can influence the balance between anti-tumor effector T cells and pro-tumor regulatory T cells (Tregs), making it a target for immune checkpoint modulation [PMID: 30108115]. Therapeutic development has focused on ICOSL antagonists, such as the monoclonal antibody prezalumab (AMG 557) and the dual-target fusion protein acazicolcept (ALPN-101), which aim to suppress aberrant T-cell and B-cell responses in chronic inflammatory conditions [ClinicalTrials.gov: NCT00774319].

Other names

ICOSLGB7-H2B7RP-1CD275GL50LICOS

Antagonism of the ICOS-ICOSL costimulatory pathway to inhibit T-cell activation and downstream B-cell mediated immune responses.