The Immune System in Hepatocellular Carcinoma and Potential New Immunotherapeutic Strategies

Author:

Bertino Gaetano1ORCID,Demma Shirin1ORCID,Ardiri Annalisa1,Proiti Maria1ORCID,Malaguarnera Giulia2ORCID,Bertino Nicoletta34,Malaguarnera Mariano5,Malaguarnera Michele26

Affiliation:

1. Department of Medical and Pediatric Sciences, Hepatology Unit, University of Catania, Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy

2. Research Centre “The Great Senescence”, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy

3. Faculty of Pharmacy, University of Catania, Viale Andrea Doria No. 6, 95123 Catania, Italy

4. Faculty of Pharmacy, University of Catania, University of Catania Policlinic, Via S. Sofia No. 78, 95123 Catania, Italy

5. Department of Medical and Pediatric Science, Research Centre “The Great Senescence”, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy

6. International Ph.D. Program in Neuropharmacology, University of Catania, Cannizzaro Hospital, Via Messina No. 829, 95100 Catania, Italy

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.Materials and 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.”Discussion and Conclusion. 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.

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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