CTLA-4 & PD-1

Every year, thousands of dogs are diagnosed with cancer. Canine cancers share many of the characteristics of human cancers, including tissue location, tumor progression, and response to chemotherapy and radiation. Unfortunately, the canine lymphocyte population is not as well defined as human lymphocytes, and reagents targeting the immune checkpoint pathway have not been widely used in veterinary research. Interruption of the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is an established and effective therapeutic strategy in human oncology and may also be effective in the treatment of canine cancers.

This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases.