Department of Internal Medicine II, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.
Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, Germany.
Nat Immunol. 2018 Mar;19(3):222-232. doi: 10.1038/s41590-018-0044-z. Epub 2018 Jan 29.
In contrast to most other malignancies, hepatocellular carcinoma (HCC), which accounts for approximately 90% of primary liver cancers, arises almost exclusively in the setting of chronic inflammation. Irrespective of etiology, a typical sequence of chronic necroinflammation, compensatory liver regeneration, induction of liver fibrosis and subsequent cirrhosis often precedes hepatocarcinogenesis. The liver is a central immunomodulator that ensures organ and systemic protection while maintaining immunotolerance. Deregulation of this tightly controlled liver immunological network is a hallmark of chronic liver disease and HCC. Notably, immunotherapies have raised hope for the successful treatment of advanced HCC. Here we summarize the roles of specific immune cell subsets in chronic liver disease, with a focus on non-alcoholic steatohepatitis and HCC. We review new advances in immunotherapeutic approaches for the treatment of HCC and discuss the challenges posed by the immunotolerant hepatic environment and the dual roles of adaptive and innate immune cells in HCC.
与大多数其他恶性肿瘤不同，肝细胞癌（HCC）几乎仅在慢性炎症的背景下发生，约占原发性肝癌的 90%。无论病因如何，慢性坏死性炎症、代偿性肝再生、肝纤维化诱导和随后的肝硬化的典型序列通常先于肝癌发生。肝脏是一种中央免疫调节剂，在维持免疫耐受的同时确保器官和全身的保护。这种严格控制的肝脏免疫网络的失调是慢性肝病和 HCC 的标志。值得注意的是，免疫疗法为晚期 HCC 的成功治疗带来了希望。在这里，我们总结了特定免疫细胞亚群在慢性肝病中的作用，重点关注非酒精性脂肪性肝炎和 HCC。我们回顾了 HCC 治疗的免疫治疗方法的新进展，并讨论了免疫耐受的肝环境以及适应性和固有免疫细胞在 HCC 中的双重作用所带来的挑战。
