title: The immune system in hepatocellular carcinoma and potential new immunotherapeutic strategies.
abstract: BACKGROUND
  Hepatocellular carcinoma is a major health problem worldwide and the third most common cause of cancer-related death. HCC treatment decisions are complex and dependent upon tumor staging. Several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Despite of only modest objective response rates according to the Response Evaluation Criteria in Solid Tumors, several studies showed encouraging results in terms of prolongation of the time to progression, disease stabilization, and survival. Cellular immunotherapy would improve the immune state and has potential in enhancing the therapeutic outcome for HCC patients.
  
  
  METHODS
  A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: "hepatocellular carcinoma," "molecular hepatocarcinogenesis," "targeted therapy," "molecular immunological targets," "tumour-associated antigens," "Tregs," "MDSCs," "immunotherapy."
  
  
  CONCLUSIONS
  Treatment strategies combining blockade of immunoregulatory cell types such as Tregs and MDSCs and of inhibitory receptors, with vaccine-induced activation of TAA-specific T cells, may be necessary to achieve the most effective therapeutic antitumour activity in HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.
authors.affiliation: Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bertino
authors.affiliation: Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy.
authors.forename: Shirin
authors.initials: S
authors.lastname: Demma
authors.affiliation: Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ardiri
authors.affiliation: Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Proiti
authors.affiliation: Liver Unit, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Abdominal Transplantation Unit, ISMETT Palermo, UPMC Italy, Via Ernesto Tricomi No. 5, 90127 Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gruttadauria
authors.affiliation: Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Toro
authors.affiliation: Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy.
authors.forename: Isidoro
authors.initials: I
authors.lastname: Di Carlo
authors.affiliation: Research Centre "The Great Senescence", University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Malaguarnera
authors.affiliation: Faculty of Pharmacy, University of Catania, Viale Andrea Doria No. 6, 95123 Catania, Italy ; Faculty of Pharmacy, University of Catania, University of Catania Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bertino
authors.affiliation: Department of Medical and Pediatric Science, Research Centre "The Great Senescence", University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Malaguarnera
authors.affiliation: Research Centre "The Great Senescence", University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy ; International Ph.D. Program in Neuropharmacology, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Malaguarnera
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*