T-cell-mediated immunotherapy is one of the four most effective methods to treat cancer, and it has shown great clinical success. Nevertheless, the current T-cell-based cancer immunotherapies are only effective in a limited group of patients. As a result, new cancer immunotherapies are needed to benefit more patients.
Prof. XU Chenqi's group and Prof. LI Boliang's group from the Institute of Biochemistry and Cell Biology (SIBCB) of the Shanghai Institutes for Biological Sciences investigated T-cell antitumor immunity from a new perspective. They hypothesized that modulating T-cell metabolism can make killer T-cells more "metabolically fit" to fight cancer cells.
The researchers found that inhibiting the cholesterol esterification enzyme ACAT1 can increase the plasma membrane cholesterol level and therefore promote T-cell signaling and the 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 an even better antitumor effect.
This study opens a new field of cancer immune therapy by identifying ACAT1 as a promising drug target.
Related work was published in Nature on March 16, 2016.
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