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The immunology of hepatocellular carcinoma

Abstract

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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Fig. 1: Role of necroinflammation in CLD and the development of HCC.

Marina Corral Spence/Springer Nature.

Fig. 2: The dual role of the adaptive immune system in hepatocarcinogenesis and HCC surveillance.
Fig. 3: Innate and adaptive immune cell subsets in NAFLD, NASH and NASH-induced HCC.

Marina Corral Spence/Springer Nature

Fig. 4: Immunological prognostic markers in HCC and possible patient stratification.

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Acknowledgements

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.).

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Ringelhan, M., Pfister, D., O’Connor, T. et al. The immunology of hepatocellular carcinoma. Nat Immunol 19, 222–232 (2018). https://doi.org/10.1038/s41590-018-0044-z

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