Frontiers in Immunology (Jun 2022)

Immune-Mediated Hepatitis During Immune Checkpoint Inhibitor cancer Immunotherapy: Lessons From Autoimmune Hepatitis and Liver Immunology

  • Julian Hercun,
  • Julian Hercun,
  • Catherine Vincent,
  • Catherine Vincent,
  • Marc Bilodeau,
  • Marc Bilodeau,
  • Pascal Lapierre,
  • Pascal Lapierre

DOI
https://doi.org/10.3389/fimmu.2022.907591
Journal volume & issue
Vol. 13

Abstract

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Immune checkpoint inhibitors (ICI) are being increasingly used to successfully treat several types of cancer. However, due to their mode of action, these treatments are associated with several immune-related adverse events (irAEs), including immune-mediated autoimmune-like hepatitis in 5 to 10% of cases. The specific immune mechanism responsible for the development of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI) is currently unknown. This review summarizes the current knowledge on hepatic irAEs during cancer immunotherapy. It also addresses the clinical management of ILICI and how it is becoming an increasingly important clinical issue. Clinical, histological, and laboratory features of autoimmune hepatitis (AIH) and ILICI are compared, and their shared and distinctive traits are discussed in an effort to better understand the development of hepatic irAEs. Finally, based on the current knowledge of liver immunology and AIH pathogenesis, we propose a series of events that could trigger the observed liver injury in ICI-treated patients. This model could be useful in the design of future studies aiming to identify the specific immune mechanism(s) at play in ILICI and improve immune checkpoint inhibitor cancer immunotherapy.

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