Bengsch Bertram, Thimme Robert
Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Germany.
Signalling Research Centres BIOSS and CIBSS, University of Freiburg.
Z Gastroenterol. 2019 Jan;57(1):74-86. doi: 10.1055/a-0805-6936. Epub 2019 Jan 14.
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.
通过检查点阻断方法进行免疫调节的成功正在改变肿瘤学，在许多癌症实体的晚期疾病患者中产生了高且持久的肿瘤反应。这些方法通过解除负反馈途径的抑制来重振适应性抗肿瘤免疫反应，在具有高新生抗原负荷的肿瘤中，对于预先存在显著T细胞反应的患者特别有效。虽然肝癌患者临床试验开始出现有前景的数据，但其潜在的免疫生物学仍知之甚少。在本综述中，我们讨论了当前检查点阻断疗法成功的免疫机制及其对肝病学的影响，包括免疫相关肝炎的管理。检查点阻断疗法为难治性肝癌提供了新的治疗选择，但也给面临免疫相关不良事件的肝病学家带来了新的临床挑战。
