B7 homolog 3 (B7-H3, CD276) is a member of the B7 family of cell surface ligands that regulate T cell activation and immune responses. B7-H3 protein contains two extracellular Ig-like V-type domains and two IgG-like C2-type domains, a transmembrane domain, and a short intracellular domain. Early research examining the biological process of B7-H3 suggested that B7-H3 is a positive regulator of T cell response. Subsequent research studies indicated that B7-H3 is a negative regulator of T cell response, and that the protein inhibits T cell proliferation. One possibility is that B7-H3 interacts with two distinct sets of receptors, resulting in seemingly opposite biological outcomes. B7-H3 is expressed by antigen presenting cells, activated T cells, and a few normal tissues, including placenta and prostate. Expression of B7-H3 is seen in several cancer types, including prostate, breast, colon, lung, and gastric cancers, and in endothelial cells from tumor associated vasculature.