{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:13:57Z","timestamp":1789740837679,"version":"4.0.1"},"reference-count":129,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>One of the most important abilities of a tumor is to establish a state of immunosuppression inside the tumor microenvironment. This is made possible through numerous mechanisms of tumor immune escape that have been identified in experimental studies during the last decades. In addition, the hepatic microenvironment is commonly oriented towards a state of immune tolerance because the liver receives blood from the hepatic arteries and portal veins containing a variety of endogenous antigens. Therefore, the hepatic microenvironment establishes an autoimmune tolerance, preventing an autoimmune reaction in the liver. On this basis, hepatic tumor cells may escape the immune system, avoiding being recognized and destroyed by immune cells. Moreover, since the etiology of Hepatocellular Carcinoma (HCC) is often related to cirrhosis, and hepatitis B or C, this tumor develops in the context of chronic inflammation. Thus, the HCC microenvironment is characterized by important immune cell infiltration. Given these data and the poor prognosis of advanced HCC, different immunotherapeutic strategies have been developed and evaluated for these patients. In this review, we describe all the clinical applications of immunotherapy for advanced HCC, from the drugs that have already been approved to the ongoing clinical trials.<\/jats:p>","DOI":"10.3390\/cancers15030654","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T04:19:22Z","timestamp":1674447562000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Immunotherapy and the Combination with Targeted Therapies for Advanced Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5074-4951","authenticated-orcid":false,"given":"Carmelo","family":"Laface","sequence":"first","affiliation":[{"name":"Medical Oncology, Dario Camberlingo Hospital, 72021 Francavilla Fontana, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girolamo","family":"Ranieri","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia Maria","family":"Maselli","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dario Camberlingo Hospital, 72021 Francavilla Fontana, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ambrogio","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Foti","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8043-6100","authenticated-orcid":false,"given":"Michele","family":"Ammendola","sequence":"additional","affiliation":[{"name":"Department of Health Science, General Surgery, Medicine School of Germaneto, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marigia","family":"Laterza","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-4316","authenticated-orcid":false,"given":"Gerardo","family":"Cazzato","sequence":"additional","affiliation":[{"name":"Department of Emergency and Organ Transplantation, Pathology Section, University of Bari \u201cAldo Moro\u201d, Piazza Giulio Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Memeo","sequence":"additional","affiliation":[{"name":"Unit of Hepato-Pancreatic-Biliary Surgery, \u201cF. Miulli\u201d General Regional Hospital, 70021 Acquaviva Delle Fonti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Mastrandrea","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Lioce","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palma","family":"Fedele","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dario Camberlingo Hospital, 72021 Francavilla Fontana, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1042\/BCJ20210233","article-title":"Immunoregulatory signal networks and tumor immune evasion mechanisms: Insights into therapeutic targets and agents in clinical development","volume":"479","author":"Wei","year":"2022","journal-title":"Biochem. 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