Icos, also known as Inducible Co-Stimulator (CD278), is a member of the B7 family and an activating costimulatory immune checkpoint expressed on activated T cells. Its ligand, ICOSL, is present on antigen-presenting cells and somatic cells. Icos plays a crucial role in the immune system, regulating T-cell activation, effector functions, and differentiation. The Icos-ICOSL binding is associated with the release of cytokines, influencing various T-cell subpopulations [2,6].

Icos has a dual role in many diseases. In immune diseases, Icos + Tregs have increased generation, proliferation, and survival abilities, with Icos-induced IL-10 contributing to their superior capacity, though the mechanism needs further study [1]. In transplantation, Icos:B7RP-1 blockade shows variable results in modulating lymphocyte proliferation and prolonging graft survival; timing, dose, and combination with other immunosuppressive treatments are important [2]. In allergic diseases, the Icos/ICOS-L axis has a dual function in the development of multiple allergic diseases [3]. In cancer, both antagonist and agonist antibodies targeting the Icos/ICOSL pathway might be of interest. Icos activation can enhance inhibitory checkpoint blockade, while its neutralization can reduce immunosuppressive Tregs' function and inhibit lymphoid tumor cells [4]. Icos-expressing CAR-T cells can effectively eradicate triple-negative breast cancer and metastasis, with ICOSL expression on TNBC cells being critical for enhancing the antitumor effects of these CAR-T cells [5,7].

In conclusion, Icos is a key regulator in the immune system, involved in multiple disease processes such as immune, allergic, and cancer diseases. The study of Icos, especially through in vivo models like KO or CKO mouse models (not specifically detailed in the given references but generally important for functional studies), helps to understand its complex role in disease development, providing potential therapeutic targets for these diseases.