The Role of Myeloid Cells in Hepatotoxicity Related to Cancer Immunotherapy.

Abstract

Simple SummaryImmune-modulating cancer treatments have proved to be highly effective in a wide range of tumour types. They interrupt the usual communication between cells in the immune system, encouraging them to become more active in identifying and destroying cancer cells. Although these therapies are very successful in treating cancer, patients frequently experience liver injury as a side effect related to over activation of the immune system. If cancer patients develop this side effect, they need to stop their cancer therapy and be given strong immunosuppressants. Researchers are now working on understanding the mechanisms involved in the development of liver inflammation. In this review we will summarise findings identifying classes of immune cells that are of particular importance in this context and highlight ways in which we can use this knowledge to improve the safety of these new cancer drugs.Drug-related hepatotoxicity is an emerging clinical challenge with the widening use of immunotherapeutic agents in the field of oncology. This is an important complication to consider as more immune oncological targets are being identified to show promising results in clinical trials. The application of these therapeutics may be complicated by the development of immune-related adverse events (irAEs), a serious limitation often requiring high-dose immunosuppression and discontinuation of cancer therapy. Hepatoxicity presents one of the most frequently encountered irAEs and a better understanding of the underlying mechanism is crucial for the development of alternative therapeutic interventions. As a novel drug side effect, the immunopathogenesis of the condition is not completely understood. In the liver, myeloid cells play a central role in the maintenance of homeostasis and promotion of inflammation. Recent research has identified myeloid cells to be associated with hepatic adverse events of various immune modulatory monoclonal antibodies. In this review article, we provide an overview of the role of myeloid cells in the immune pathogenesis during hepatoxicity related to cancer immunotherapies and highlight potential treatment options.