Gudd Cathrin L C, Possamai Lucia A
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Department of Metabolism, Digestion & Reproduction, Imperial College London, London SW7 2AZ, UK.
Cancers (Basel). 2022 Apr 10;14(8):1913. doi: 10.3390/cancers14081913.
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.
随着免疫治疗药物在肿瘤学领域的广泛应用，药物相关肝毒性成为一个新出现的临床挑战。鉴于越来越多的免疫肿瘤靶点在临床试验中显示出有前景的结果，这是一个需要考虑的重要并发症。这些疗法的应用可能会因免疫相关不良事件（irAEs）的发生而变得复杂，这是一个严重的限制，常常需要大剂量免疫抑制并中断癌症治疗。肝毒性是最常出现的irAEs之一，更好地理解其潜在机制对于开发替代治疗干预措施至关重要。作为一种新的药物副作用，该病症的免疫发病机制尚未完全明确。在肝脏中，髓样细胞在维持内环境稳定和促进炎症方面发挥着核心作用。最近的研究已确定髓样细胞与各种免疫调节单克隆抗体的肝脏不良事件有关。在这篇综述文章中，我们概述了髓样细胞在癌症免疫治疗相关肝毒性的免疫发病机制中的作用，并强调了潜在的治疗选择。
