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胆固醇代谢:癌细胞与免疫微环境的十字路口。

Cholesterol metabolism: At the cross road between cancer cells and immune environment.

机构信息

Department of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy.

Department of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy.

出版信息

Int J Biochem Cell Biol. 2020 Dec;129:105876. doi: 10.1016/j.biocel.2020.105876. Epub 2020 Nov 6.

Abstract

Mevalonate pathway is a highly conserved pathway that produces isoprenoids and cholesterol, and it is often increased in cancer cells. Cholesterol, upstream metabolites including isoprenoids and cholesterol derivatives such as oxysterols modulate cell proliferation, motility, stemness and drug resistance. Moreover, when produced by cancer cells or immune infiltrating cells, they modulate the activity of immune populations of the tumor microenvironment. In this review, we will focus on the recent findings demonstrating that cholesterol derivatives may regulate tumor immune recognition or immune escape, playing a critical role in the immune surveillance. Since the mevalonate pathway is druggable, a deeper knowledge of the metabolic cross talks existing between the mevalonate pathway of cancer cells and immune cells may help to identify novel agents targeting cholesterol metabolism, able to boost the anti-tumor activity of the immune populations.

摘要

甲羟戊酸途径是一条高度保守的途径,可产生异戊烯和胆固醇,其在癌细胞中通常会增加。胆固醇、上游代谢物包括异戊烯和胆固醇衍生物(如氧化固醇)调节细胞增殖、运动性、干细胞特性和耐药性。此外,当由癌细胞或免疫浸润细胞产生时,它们调节肿瘤微环境中免疫群体的活性。在这篇综述中,我们将重点介绍最近的发现,这些发现表明胆固醇衍生物可能调节肿瘤免疫识别或免疫逃逸,在免疫监视中发挥关键作用。由于甲羟戊酸途径是可用药的,因此深入了解癌细胞和免疫细胞之间存在的代谢交叉对话可能有助于确定靶向胆固醇代谢的新型药物,从而增强免疫群体的抗肿瘤活性。

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