Eggert Tobias, Greten Tim F
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Pharmacol Ther. 2017 May;173:47-57. doi: 10.1016/j.pharmthera.2017.02.005. Epub 2017 Feb 4.
The tumor microenvironment (TME) in the liver plays an important role in primary and metastatic liver tumor formation and tumor growth promotion. Cellular and non-cellular components of the TME significantly influence tumor development, growth, metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular components of the TME in the liver not only consist of infiltrating immune cells, but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC), which promote tumor growth by negatively regulating tumor-associated immune responses. In this review, we characterize cells of the TME with pro- and anti-tumor function in primary and metastatic liver tumors. Furthermore, we summarize mechanisms that permit growth of hepatic tumors despite the occurrence of spontaneous anti-tumor immune responses and how novel therapeutic approaches targeting the TME could unleash tumor-specific immune responses to improve survival of liver cancer patients.
肝脏中的肿瘤微环境（TME）在原发性和转移性肝肿瘤的形成以及促进肿瘤生长方面发挥着重要作用。TME的细胞和非细胞成分显著影响肿瘤的发展、生长、转移扩散、抗肿瘤免疫以及对肿瘤治疗的反应。肝脏中TME的细胞成分不仅包括浸润的免疫细胞，还包括肝脏驻留细胞，如肝窦内皮细胞（LSEC）和肝星状细胞（HSC），它们通过负向调节肿瘤相关免疫反应来促进肿瘤生长。在本综述中，我们描述了原发性和转移性肝肿瘤中具有促肿瘤和抗肿瘤功能的TME细胞。此外我们还总结了尽管发生了自发的抗肿瘤免疫反应但仍能使肝肿瘤生长的机制，以及针对TME的新型治疗方法如何释放肿瘤特异性免疫反应以提高肝癌患者的生存率。
