Z Gastroenterol 2019; 57(01): 74-86
DOI: 10.1055/a-0805-6936
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Success of immune checkpoint blockade therapies – mechanisms and implications for hepatology

Erfolge der Immuntherapien mit Checkpoint Blockade Antikörpern – Mechanismen und Implikationen für die Hepatologie
Bertram Bengsch
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Germany
2   Signalling Research Centres BIOSS and CIBSS, University of Freiburg
,
Robert Thimme
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Germany
› Author Affiliations
Further Information

Publication History

23 September 2018

21 November 2018

Publication Date:
14 January 2019 (online)

Abstract

The success of immune modulation by checkpoint blockade approaches is currently transforming oncology, with high and long-lasting tumor responses in patients with advanced disease across many cancer entities. Rooted in the reinvigoration of adaptive antitumor immune responses through disinhibition of negative feedback pathways, these approaches are particularly effective in patients with significant preexisting T cell responses in tumors with high neoantigen load. While promising data is starting to emerge from clinical trials in liver cancer patients, the underlying immunobiology remains poorly understood. In this review, we discuss the immunological mechanisms underlying the success of current checkpoint blockade therapies and the implications for hepatology including management of immune-related hepatitis. Checkpoint blockade therapy provides novel therapeutic options for difficult-to-treat liver cancers but also novel clinical challenges for hepatologists facing immune-related adverse events.

Zusammenfassung

Die Erfolge der Immuntherapien mit Checkpoint Blockade Antikörpern revolutionieren aktuell die Behandlung maligner Erkrankungen. Für eine Vielzahl von Tumorentitäten kann bei Patienten mit bereits fortgeschrittener Erkrankung ein starkes und langandauerndes Tumoransprechen erreicht werden. Dieses Ansprechen ist begründet durch die Verstärkung adaptiver gegen den Tumor gerichteter Immunantworten und wird durch eine Enthemmung negativer immunologischer Feedbacksignale erreicht. Besonders effektiv sind die Therapien bei Patienten mit Tumoren, die eine große Zahl von Neoantigenen aufweisen. Klinische Studien zur Anwendung von Checkpoint Blockade Therapien bei Patienten mit Lebertumoren haben bereits vielversprechende Ergebnisse gezeigt, jedoch ist die zugrunde liegende Immunbiologie noch unzureichend verstanden. Die zunehmende Anwendung von Immuntherapien stellt Hepatologen aber auch vor neue klinische Herausforderungen wenn Immun-vermittelte Nebenwirkungen auftreten. In dieser Übersichtsarbeit diskutieren wir daher die immunologischen Mechanismen, die für den Erfolg von Checkpoint Blockade Therapien verantwortlich sind, ihre Implikationen für die Hepatologie und das Management der Immun-vermittelten Hepatitis unter Checkpoint Blockade Behandlung. Insgesamt stellen Immuntherapien neue und aussichtsreiche Behandlungsoptionen für schwer zu behandelnde Entitäten wie Lebertumoren dar.

 
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