Refolo Maria Grazia, Messa Caterina, Guerra Vito, Carr Brian Irving, D'Alessandro Rosalba
Laboratory of Cellular and Molecular Biology, Department of Clinical Pathology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, 70013 Castellana Grotte, BA, Italy.
Clinical Trial Unit, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, 70013 Castellana Grotte, BA, Italy.
Cancers (Basel). 2020 Mar 10;12(3):641. doi: 10.3390/cancers12030641.
HCC (hepatocellular carcinoma) is the second leading cause of cancer deaths worldwide, with several etiologic causes, mostly inflammation-associated. Different inflammatory responses in the liver can be triggered by different etiological agents. The inflammatory process can be resolved or be persistent, depending on the etiology and multiple other factors. Chronic inflammation, tissue remodeling, genetic alterations, and modifications in cellular signaling are considered to be key processes promoting immunosuppression. The progressive immunosuppression leads to the inactivation of anti-tumor immunity involved in HCC carcinogenesis and progression. Tumor cellular processes including DNA damage, necrosis, and ER (endoplasmic reticulum) stress can affect both immune-surveillance and cancer-promoting inflammation, supporting a mutual interdependence. Here, we review the current understanding of how chronic liver injury and inflammation is triggered and sustained, and how inflammation is linked to HCC. The identification of many hepatic microenvironmental inflammatory processes and their effector molecules, has resulted in extensive translational work and promising clinical trials of new immunomodulatory agents.
肝细胞癌（HCC）是全球第二大致癌死亡原因，有多种病因，大多与炎症相关。不同的致病因素可引发肝脏不同的炎症反应。炎症过程可能得到解决，也可能持续存在，这取决于病因和多种其他因素。慢性炎症、组织重塑、基因改变以及细胞信号传导的改变被认为是促进免疫抑制的关键过程。进行性免疫抑制导致参与HCC发生和发展的抗肿瘤免疫失活。肿瘤细胞过程，包括DNA损伤、坏死和内质网（ER）应激，可影响免疫监视和促癌炎症，支持相互依存关系。在此，我们综述了目前对慢性肝损伤和炎症如何引发及持续存在，以及炎症如何与HCC相关联的理解。对许多肝脏微环境炎症过程及其效应分子的鉴定，已经带来了广泛的转化研究工作和有前景的新型免疫调节药物临床试验。
