title: CTLA-4 blockade and the renaissance of cancer immunotherapy.
abstract: Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) plays a key role in restraining the adaptive immune response of T-cells towards a variety of antigens including tumor associated antigens (TAAs). The blockade of this immune checkpoint elicits an effective anticancer immune response in a range of preclinical models, suggesting that naturally occurring (or therapeutically induced) TAA specific lymphocytes need to be "unleashed" in order to properly fight against malignant cells. Therefore, investigators have tested this therapeutic hypothesis also in humans: the favorable results obtained with this strategy in patients with advanced cutaneous melanoma are revolutionizing the management of this highly aggressive disease and are fueling new enthusiasm on cancer immunotherapy in general. Here we summarize the biology of CTLA-4, overview the experimental data supporting the rational for targeting CTLA-4 to treat cancer and review the main clinical findings on this novel anticancer approach. Moreover, we critically discuss the current challenges and potential developments of this promising field of cancer immunotherapy.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy. Electronic address: simone.mocellin@unipd.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Mocellin
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D060908:CTLA-4 Antigen
keywords: CTLA-4; Cancer; Co-inhibitory molecule; Co-signaling; Immunotherapy; Tumor immunology