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ICOS (Inducible Co-Stimulator, CD278) is a member of the CD28 family that regulates T cell activity and immune responses. The ICOS protein contains an extracellular IgV like domain, a transmembrane domain, and an intracellular domain with a YMFM motif. ICOS is primarily expressed on activated CD4+ and CD8+ T cells. Upon binding to its ligand, ICOS potentiates the T cell response to antigen through activation of the PI3K signaling pathway). In addition to enhancing T cell activation and proliferation, ICOS plays an important role in the regulation of T follicular helper cells. Research studies suggest that ICOS is a potential therapeutic target, and could serve as a prognostic biomarker for neoplastic therapy involving CTLA-4 blockade.