title: Basics of PD-1 in self-tolerance, infection, and cancer immunity.
abstract: Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as "checkpoints" of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD-1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule.
authors: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, East Lecture Hall 4F, Shinjuku-ku, Tokyo, 160-8582, Japan. schikuma@keio.jp.
authors: Shunsuke
authors: S
authors: Chikuma
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology* / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor
keywords: CTLA-4; Costimulation; Immune checkpoint blockade; Immune tolerance; PD-1; T lymphocytes