title: The blockade of immune checkpoints in cancer immunotherapy.
abstract: Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
authors.affiliation: Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, CRB1 Room 444, 1650 Orleans Street, Baltimore, Maryland 21287, USA. dpardol1@jhmi.edu
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000502:physiology; D019496:Cancer Vaccines / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000502:physiology; D019139:Tumor Escape
chemical_list: D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor