B7-H1, also known as PD-L1 and CD274, is an approximately 65 kDa transmembrane glycoprotein in the B7 family of immune regulatory molecules (1, 2). Mature cynomolgus B7-H1 consists of a 220 amino acid (aa) extracellular domain (ECD) with two immunoglobulin-like domains, a 21 aa transmembrane segment, and a 30 aa cytoplasmic domain. Within the ECD, cynomolgus B7-H1 shares 92%, 72%, and 72% aa sequence identity with human, mouse, and rat B7-H1, respectively. In addition, cynomolgus B7-H1 shares 98%, 94%, 94%, 88%, 78%, 98%, 95%, 94%, and 94% aa sequence identity with rhesus macaque, chimpanzee, sumatran orangutan, white-tufted-ear marmoset, Garnett's greater bushbaby, olive baboon, green monkey, western lowland gorilla, and northern white-cheeked gibbon B7-H1, respectively. B7-H1 is expressed on inflammatory-activated immune cells including macrophages, T cells, and B cells (3-6), keratinocytes (7, 8), endothelial and intestinal epithelial cells (8, 10), as well as a variety of carcinomas and melanoma (10, 11). B7-H1 is a B7 ligand and binds to B7-1/CD80 and PD-1 receptors on T cells (6, 7, 11-14). It suppresses T cell activation and proliferation (4, 7, 13, 15) and induces the apoptosis of activated T cells (10). It plays a role in the development of immune tolerance by promoting T cell anergy (6, 13) and enhancing regulatory T cell development (15). B7-H1 favors the development of
anti-inflammatory IL-10 and IL-22 producing dendritic cells (4, 9) and inhibits the development of Th17 cells (15). In cancer, B7-H1 provides resistance to T cell mediated lysis, enhances EMT, and enhances the tumorigenic function of Th22 cells (5, 8, 11, 14). B7-H1/PD-1 coinhibitory pathway was exploited therapeutically resulting in remarkable outcomes with 20-90% response in various types of cancer (16).