New Zealand Liver Transplant Unit, Level 15, Support Building, Auckland City Hospital, Private Bag 92024, Auckland, 1023, New Zealand.
Centenary Institute, The University of Sydney, Sydney, Locked Bag 6, Newtown, NSW, 2042, Australia.
Hepatol Int. 2020 Dec;14(6):947-957. doi: 10.1007/s12072-020-10104-3. Epub 2020 Nov 13.
Hepatocellular carcinoma (HCC) is a heterogeneous inflammation-driven malignancy, which, despite significant advances in management, continues to portend a poor prognosis. Recent advances in basic and translational research have increasingly defined the role of the tumor microenvironment in the development and progression of HCC and facilitated the development of novel molecular targets. The hepatoma microenvironment is characterised by an immunosuppressive milieu of immune cells and tumor vasculature that is both structurally and functionally abnormal. Normalising the tumor microenvironment by adopting a multipronged approach that targets both carcinogenic processes and the immunosuppressive milieu has been supported by pre-clinical and clinical data. In this review, we summarise the current understanding of the hepatoma microenvironment, its influences and dynamic interactions with tumor cells, the vasculature and the gut. Finally, we discuss how manipulating the tumor microenvironment continues to shape the evolving landscape of HCC therapy.
肝细胞癌(HCC)是一种异质性炎症驱动的恶性肿瘤,尽管在治疗方面取得了重大进展,但预后仍然不佳。基础和转化研究的最新进展越来越明确了肿瘤微环境在 HCC 的发生和发展中的作用,并促进了新型分子靶点的开发。肝癌微环境的特征是免疫细胞和肿瘤血管的免疫抑制环境,其结构和功能均异常。通过采用靶向致癌过程和免疫抑制环境的多管齐下的方法使肿瘤微环境正常化,这一策略得到了临床前和临床数据的支持。在这篇综述中,我们总结了目前对肝癌微环境的认识,包括其对肿瘤细胞、血管和肠道的影响及其动态相互作用。最后,我们讨论了如何通过操纵肿瘤微环境继续塑造 HCC 治疗的不断发展的格局。