{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T23:05:07Z","timestamp":1772060707022,"version":"3.50.1"},"reference-count":119,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"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>Background: Hepatocellular carcinoma (HCC) still represents a human tumor entity with very limited therapeutic options, especially for advanced stages. Here, immune checkpoint modulating drugs alone or in combination with local ablative techniques could open a new and attractive therapeutic \u201cdoor\u201d to improve outcome and response rate for patients with HCC. Methods: Published data on HCC experimental to pre-(clinical) treatment strategies from standard of care to novel immunomodulatory concepts were summarized and discussed in detail. Results: Overall, our knowledge of the role of immune checkpoints in HCC is dramatically increased in the last years. Experimental and pre-clinical findings could be translated to phase 1 and 2 clinical trials and became standard of care. Local ablative techniques of HCC could improve the effectivity of immune checkpoint inhibitors in situ. Conclusions: This review demonstrates the importance of immunomodulatory treatment strategies of HCC, whereby the \u201cbest treatment code\u201d of immune checkpoint drugs, combination with ablative techniques and of timing must be evaluated in coming clinical trials.<\/jats:p>","DOI":"10.3390\/cancers13071558","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T04:29:14Z","timestamp":1616992154000},"page":"1558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Immunmodulatory Treatment Strategies of Hepatocellular Carcinoma: From Checkpoint Inhibitors Now to an Integrated Approach in the Future"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8263-6288","authenticated-orcid":false,"given":"Matthias","family":"Ocker","sequence":"first","affiliation":[{"name":"Department of Gastroenterology (Campus Benjamin Franklin), Charit\u00e9 University Medicine Berlin, 10117 Berlin, Germany"},{"name":"Translational Medicine &amp; Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 55216 Ingelheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Mayr","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Department of Internal Medicine I, Paracelsus Medical University, University Hospital Salzburg (SALK), 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Kiesslich","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Department of Internal Medicine I, Paracelsus Medical University, University Hospital Salzburg (SALK), 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3297-5801","authenticated-orcid":false,"given":"Sebastian","family":"Stintzing","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, and Tumor Immunology (Campus Charit\u00e9 Mitte), Medical Department, Charit\u00e9 University Medicine Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Neureiter","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Paracelsus Medical University, University Hospital Salzburg (SALK), 5020 Salzburg, Austria"},{"name":"Cancer Cluster Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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