
AsianScientist (Mar. 28, 2016) – Researchers from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, have found that inhibiting cholesterol biosynthesis can make antitumor activity of killer T-cells more effective. Improving T-cell function in this manner can be used as a complement to current cancer immunotherapies. This study was published in Nature.
Reactivating the antitumor effects of T-cells has shown great clinical benefits in treating various cancers. However, tumors can escape T-cell attack through various mechanisms in the tumor microenvironment, and as such, current T-cell-based cancer immunotherapies are only effective in a limited group of patients. Therefore, there is a growing need for new cancer immunotherapies.
The researchers set out to investigate T-cell antitumor immunity from a new perspective: they believe that regulating cholesterol 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. A small molecule inhibitor of ACAT1, avasimibe, was used to treat cancer in mouse tumor models and showed good antitumor effect. A combination of avasimibe and anti-PD-1 antibody, a checkpoint blockade drug, showed even greater antitumor effects.
This study opens a new field of cancer immunotherapy and identifies ACAT1 as a promising drug target for cancer immunotherapy. It is worth mentioning that avasimibe was tested in clinical trials to treat atherosclerosis and had a good human safety profile.
The article can be found at: Yang et al. (2016) Potentiating the Antitumour Response of CD8+ T Cells by Modulating Cholesterol Metabolism.
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Source: Chinese Academy of Sciences; Photo: NIAID/Flickr/CC.
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