Review Article | Published:

The immunology of hepatocellular carcinoma

Nature Immunologyvolume 19pages222232 (2018) | Download Citation



In contrast to most other malignancies, hepatocellular carcinoma (HCC), which accounts for approximately 90% of primary liver cancers, arises almost exclusively in the setting of chronic inflammation. Irrespective of etiology, a typical sequence of chronic necroinflammation, compensatory liver regeneration, induction of liver fibrosis and subsequent cirrhosis often precedes hepatocarcinogenesis. The liver is a central immunomodulator that ensures organ and systemic protection while maintaining immunotolerance. Deregulation of this tightly controlled liver immunological network is a hallmark of chronic liver disease and HCC. Notably, immunotherapies have raised hope for the successful treatment of advanced HCC. Here we summarize the roles of specific immune cell subsets in chronic liver disease, with a focus on non-alcoholic steatohepatitis and HCC. We review new advances in immunotherapeutic approaches for the treatment of HCC and discuss the challenges posed by the immunotolerant hepatic environment and the dual roles of adaptive and innate immune cells in HCC.

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Supported by Else-Kröner-Stiftung (M.R., as a member of the Else-Kröner-Forschungskolleg München “Microbial triggers in disease development”), Deutsche Forschungsgemeinschaft (5892/5-1 to T.O.) and the European Research Council (consolidator grant HepatoMetaboPath to M.H.; SFBTR36, SFBTR179 and SFBTR209 to M.H.; and the European Union’s Horizon 2020 research and innovation programme (under grant agreement 667273), for M.H.).

Author information


  1. Department of Internal Medicine II, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany

    • Marc Ringelhan
  2. Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, Germany

    • Marc Ringelhan
    •  & Tracy O’Connor
  3. German Center for Infection Research (DZIF), partner site Munich, Munich, Germany

    • Marc Ringelhan
  4. Division of Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg, Germany

    • Dominik Pfister
    •  & Mathias Heikenwalder
  5. Institute of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany

    • Tracy O’Connor
    •  & Mathias Heikenwalder
  6. The Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel Canada and Department of Pathology, Hebrew University–Hadassah Medical School, Jerusalem, Israel

    • Eli Pikarsky


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The authors declare no competing financial interests.

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Correspondence to Mathias Heikenwalder.

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