胆固醇与抗肿瘤免疫

发表在《自然》杂志上的这项研究发现，通过调控细胞内的胆固醇代谢途径，可提高细胞毒T细胞的活性，从而对肿瘤细胞有效杀伤。胆固醇酯化酶-1（ACAT-1）以及胆固醇酯化酶-2（ACAT-2）是在细胞内胆固醇代谢过程中调节T细胞活性的关键性酶。

ACAT-1在细胞中普遍存在，而ACAT-2则仅肝脏以及肠道细胞中表达。它们均可促进胆固醇酯化后进行储存，但这一过程并不能增加细胞膜上胆固醇的含量。

细胞内的胆固醇是细胞生理代谢过程一类重要的物质。CD8+T细胞（又名杀伤性T细胞）是获得性免疫应答的一种细胞。在CD8+T细胞活化以及增殖过程中，需要大量的胆固醇。如果抑制ACAT酶，即可使细胞存储胆固醇的能力下降，为T细胞提供更多的游离胆固醇。利用基因工程技术敲除ACAT1基因，可抑制细胞内的胆固醇酯化。CD8+T细胞的质膜胆固醇水平上调，可增加其活力，进而更有效地对肿瘤细胞进行杀伤。

http://www.boxun.com/news/gb/health/2016/03/201603181439.shtml#.Vu1e0jr2bIU

 

Their research, entitled "Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism," was published in Nature on March 17.

The researchers investigated T-cell antitumor immunity from a new perspective. They believe that modulating T-cell metabolism can make killer T cells more "metabolically fit" to fight tumor cells. As a key component of membrane lipids, cholesterol is important for T-cell signaling and function.

Scientists found that inhibiting the cholesterol esterification enzyme ACAT1 can increase the plasma membrane cholesterol level and therefore promote the T-cell signaling and killing process.

http://www.news-medical.net/news/20160318/Inhibiting-cholesterol-esterification-can-potentiate-antitumor-activity-of-killer-T-cells.aspx