NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy

Matthias Pinter, David J. Pinato, Pierluigi Ramadori, Mathias Heikenwalder

Research output: Contribution to journalReview articlepeer-review

Abstract

The last 10 years have revolutionized our basic understanding of nonalcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining, or exacerbating nonalcoholic steatohepatitis (NASH)—a disease that has been recently defined as autoaggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carcinoma (HCC). Preliminary data from preclinical studies suggest that immunotherapy efficacy may be reduced in NASH-related HCC compared with viral HCC; however, conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with carcinogenesis and therapeutic resistance is key to prevent progression to cirrhosis, improve monitoring and stratification of NASH according to predicted cancer risk, and ultimately increase survival of patients with NASH-HCC. In this review, we summarize the state of the art in the field of NASH and NASH-HCC with focus on immunobiology. We discuss preclinical and clinical findings underpinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulnerabilities in NASH-associated HCC.

Original languageEnglish
Pages (from-to)513-520
Number of pages8
JournalClinical Cancer Research
Volume29
Issue number3
DOIs
Publication statusPublished - 1 Feb 2023

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