title: Coinhibitory molecules in cancer biology and therapy.
abstract: The adaptive immune response is controlled by checkpoints represented by coinhibitory molecules, which are crucial for maintaining self-tolerance and minimizing collateral tissue damage under physiological conditions. A growing body of preclinical evidence supports the hypothesis that unleashing this immunological break might be therapeutically beneficial in the fight against cancer, as it would elicit an effective antitumor immune response. Remarkably, recent clinical trials have demonstrated that this novel strategy can be highly effective in the treatment of patients with cancer, as shown by the paradigmatic case of ipilimumab (a monoclonal antibody blocking the coinhibitory molecule cytotoxic T lymphocyte associated antigen-4 [CTLA4]) that is opening a new era in the therapeutic approach to a chemoresistant tumor such as cutaneous melanoma. In this review we summarize the biology of coinhibitory molecules, overview the experimental and clinical attempts to interfere with these immune checkpoints to treat cancer and critically discuss the challenges posed by such a promising antitumor modality.
authors: Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128 Padova, Italy. simone.mocellin@unipd.it
authors: Simone
authors: S
authors: Mocellin
authors: Clara
authors: C
authors: Benna
authors: Pierluigi
authors: P
authors: Pilati
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D064446:Orexin Receptors; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000276:immunology
chemical_list: D000954:Antigens, Surface; C482586:BTLA protein, human; C477337:CD200R1 protein, human; D060908:CTLA-4 Antigen; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D064446:Orexin Receptors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human