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

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.

Hepatitis durch Checkpunkt-Therapie – periphere Immunaktivierung als möglicher Biomarker

“…Eine engmaschige Überwachung ist notwendig, um gerade bei höhergradigen Toxizitäten und Ausschluss von Differenzialdiagnosen rechtzeitig eine konsequente immunsuppressive Therapie durchzuführen und tödliche Verläufe abzuwenden. Die Checkpunkt-Immunhepatitis (CPI-Hep) stellt hierbei im Vergleich zu anderen betroffenen Organsystemen eine Herausforderung dar, da sie relativ häufig auftritt (etwa 30% unter Anti-PD-1/CTLA-4-Kombinationstherapie), erst spät symptomatisch wird und mit einer signifikanten Mortalität (etwa 20% der immunvermittelten Todesfälle) assoziiert ist [1]. Die Pathophysiologie der Erkrankung und insbesondere die beteiligten Immunpopulationen sind aktuell nur oberflächlich verstanden.…”

Is PD-1 blockade a potential therapy for HBV?

“…An HBV cure of any type should have a very favourable riskbenefit ratio. The potential harms and effectiveness [26][27][28] of ICI blockade will require careful tailoring and monitoring. The development of ex vivo immunological assays, as described in the paper by Martinez, will be useful.…”