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

The Inducible T-cell costimulator (ICOS) and its ligand (ICOSL) interaction is a key costimulatory pathway within the B7-CD28 superfamily that regulates adaptive immune responses (UniProt Q9Y6W8, O75144). ICOS is primarily expressed on activated T cells, while ICOSL is found on antigen-presenting cells, such as B cells and dendritic cells, as well as on some non-immune and tumor cells (PubMed 34154613). This interaction is essential for the formation of germinal centers, the differentiation of follicular helper T (Tfh) cells, and the production of high-affinity antibodies (PubMed 33033241). In the context of oncology, the pathway is targeted with agonists like feladilimab to stimulate anti-tumor T-cell activity or with antagonists like MEDI-570 to deplete immunosuppressive regulatory T cells (Tregs) (PubMed 34154613, 29535204). Conversely, in autoimmune and inflammatory diseases, blocking this interaction with agents like prezalumab can reduce the activity of pathogenic T cells and the production of autoantibodies (PubMed 33033241). Clinical trials have explored both agonists and antagonists, though some candidates have faced challenges regarding efficacy and safety, including hepatotoxicity (PubMed 34154613). Despite these hurdles, the ICOS-ICOSL axis remains a prominent target for combination therapies with other immune checkpoint inhibitors.

Other names

CD278CD275B7-H2B7RP-1GL50LICOSAILIMInducible T-cell costimulator (ICOS)Inducible T-cell costimulator ligand (ICOSL)

Agonism to enhance anti-tumor T-cell activity; Antagonism to suppress autoimmune T-cell activity or deplete regulatory T-cells.