Inducible T-cell costimulator receptor (ICOS) (ICOS)

Inducible T-cell costimulator (ICOS), also known as CD278, is a member of the CD28/CTLA-4 family of cell-surface receptors expressed primarily on activated T cells, including CD4+ and CD8+ subsets [2, 5, 6]. It plays a critical role in the adaptive immune system by providing a potent costimulatory signal upon binding to its ligand, ICOSL (B7-H2), which is constitutively expressed on B cells and can be induced on other antigen-presenting cells [5, 10]. This interaction is essential for T-cell proliferation, survival, and the production of cytokines such as IL-4 and IL-10, and it is particularly vital for the differentiation of T follicular helper (Tfh) cells and the formation of germinal centers [5, 6, 12]. In oncology, ICOS is targeted by agonist antibodies to enhance anti-tumor immunity, often showing synergy when combined with other checkpoint inhibitors like anti-PD-1 or anti-CTLA-4 [11, 13, 15]. Conversely, in autoimmune and inflammatory diseases, the ICOS pathway is often overactive, making it a target for antagonistic therapies designed to dampen excessive immune responses [1, 3, 17]. Additionally, ICOS is highly expressed in certain T-cell lymphomas, where it serves as a target for therapeutic depletion of malignant cells [6, 11].

Other names

CD278AILIMActivation-inducible lymphocyte immunomediatory moleculeCVID1Inducible costimulator

ICOS agonists bind to the receptor on activated T cells to stimulate costimulatory signaling pathways, such as PI3K/AKT, thereby enhancing T-cell proliferation, survival, and effector functions [1, 11]. ICOS antagonists or inhibitors block the interaction between ICOS and its ligand (ICOSL), preventing T-cell overactivation in autoimmune diseases or inducing the depletion of ICOS-expressing malignant T cells via antibody-dependent cellular cytotoxicity (ADCC) [3, 6, 11].