ICOS

Inducible co-stimulator (ICOS), a member of the CD28/CTLA-4 immunoglobulin superfamily, is a specific T cell co-stimulatory molecule which activates T cells upon binding to its ligand (ICOS-L). It is present on the T cell surface as a disulfide bond-linked homodimer and it is rapidly up-regulated upon TCR cross-linking and/or CD28 co-stimulation.
ICOSL (also called B7-H2, B7RP-1, LICOS, and GL50) is weakly expressed on antigen-presenting cells in the steady state and is up-regulated after activation of these cells. ICOSL is also expressed on somatic cells, including tumor cells in the tumor microenvironment. The ICOS-ICOSL pathway promotes T-cell activation, differentiation, and effector responses, and T cell-dependent B-cell responses. The activated T cells leads predominantly to the production of effector cytokines such as IL-4 and IL-10 and, to a lesser extent, IL-2, IFN-γ, and TNF-α, thereby playing a more important role in Th2 responses than Th1 responses. ICOS co-stimulation controls tumor immunity on two different sides. On one hand, ICOS promotes the activation of anti-tumor cytotoxic T cells. On the other hand, the promoting role for Tregs has an unfavourable outcome for tumor immunity. Tregs inhibit the innate and adaptive immune cells primarily through the secretion of IL-10 and TGF-β.