Inducible T-cell costimulator (ICOS) (ICOS)

Inducible T-cell costimulator (ICOS), also known as CD278, is a member of the CD28/CTLA-4 family of costimulatory receptors expressed on the surface of activated T cells [5, 10]. Unlike CD28, which is constitutively expressed, ICOS is upregulated only after T-cell receptor (TCR) engagement, making it a specific marker of T-cell activation [1, 16]. It plays a critical role in the development and maintenance of T follicular helper (Tfh) cells, germinal center formation, and the production of cytokines such as IL-4 and IL-21, which are essential for B-cell antibody responses [2, 7, 13]. In oncology, ICOS is a target for agonistic antibodies designed to enhance anti-tumor immunity, often in combination with PD-1 or CTLA-4 inhibitors, although its high expression on regulatory T cells (Tregs) can lead to unintended immunosuppression [2, 8, 11]. Conversely, ICOS antagonists or depleting antibodies are being explored for the treatment of autoimmune diseases like systemic lupus erythematosus and T-cell lymphomas where ICOS signaling drives pathogenesis [1, 12, 16].

Other names

CD278AILIMActivation-inducible lymphocyte immunomediatory moleculeInducible costimulatorCVID1

Agonism of ICOS signaling to enhance effector T-cell function; Antagonism to block costimulation in autoimmunity; Antibody-dependent cellular cytotoxicity (ADCC) to deplete ICOS-positive cells [2, 8, 11, 16].