State Key Laboratory of Molecular Biology, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
Nat Metab. 2020 Feb;2(2):132-141. doi: 10.1038/s42255-020-0174-0. Epub 2020 Feb 10.
Cholesterol metabolism produces essential membrane components as well as metabolites with a variety of biological functions. In the tumour microenvironment, cell-intrinsic and cell-extrinsic cues reprogram cholesterol metabolism and consequently promote tumourigenesis. Cholesterol-derived metabolites play complex roles in supporting cancer progression and suppressing immune responses. Preclinical and clinical studies have shown that manipulating cholesterol metabolism inhibits tumour growth, reshapes the immunological landscape and reinvigorates anti-tumour immunity. Here, we review cholesterol metabolism in cancer cells, its role in cancer progression and the mechanisms through which cholesterol metabolites affect immune cells in the tumour microenvironment. We also discuss therapeutic strategies aimed at interfering with cholesterol metabolism, and how the combination of such approaches with existing anti-cancer therapies can have synergistic effects, thus offering new therapeutic opportunities.
胆固醇代谢产生必需的膜成分以及具有多种生物学功能的代谢物。在肿瘤微环境中，细胞内和细胞外的信号重新编程胆固醇代谢，从而促进肿瘤发生。胆固醇衍生的代谢物在支持癌症进展和抑制免疫反应方面发挥着复杂的作用。临床前和临床研究表明，操纵胆固醇代谢可以抑制肿瘤生长、重塑免疫景观并重新激活抗肿瘤免疫。在这里，我们综述了癌细胞中的胆固醇代谢、它在癌症进展中的作用以及胆固醇代谢物影响肿瘤微环境中免疫细胞的机制。我们还讨论了旨在干扰胆固醇代谢的治疗策略，以及这些方法与现有的抗癌疗法相结合如何产生协同效应，从而为新的治疗机会提供了可能。
