The CD275 antigen, also known as inducible T-cell costimulator ligand (ICOS-L) or B7 homolog 2 (B7-H2), is a transmembrane protein belonging to the B7 family of immune regulatory molecules. It is expressed on antigen-presenting cells (APCs), such as dendritic cells, B cells, and macrophages, as well as certain non-hematopoietic cells. CD275 interacts with its receptor ICOS (CD278) on activated T cells, delivering a critical co-stimulatory signal that amplifies T-cell proliferation, cytokine production, and effector functions. This interaction plays a dual role in immune regulation: it supports T-cell activation in anti-pathogen or anti-tumor responses but may also promote immune tolerance in chronic inflammation or cancer.
CD275 antibodies are tools or therapeutics designed to modulate this pathway. Antagonistic antibodies blocking CD275/ICOS binding are explored to inhibit overactive T-cell responses in autoimmune diseases. Conversely, agonistic antibodies may enhance T-cell activity for cancer immunotherapy. Research highlights CD275's involvement in T follicular helper (Tfh) cell differentiation, germinal center formation, and regulatory T-cell (Treg) function, linking it to autoimmune disorders, transplant rejection, and tumor immune evasion. Its dynamic expression in tumor microenvironments makes CD275 a promising biomarker and target for immune checkpoint therapies. Current studies focus on optimizing antibody specificity and evaluating combinatorial approaches with PD-1/PD-L1 inhibitors to overcome resistance in immuno-oncology.