Chinese scientists discover new ways to improve T cell anti-tumor immunity
March 25, 2016 Source: Bio Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];State Key Laboratory of Molecular Biology, National Institute of Biochemistry and Cell Biology, Shanghai Institute of Biosciences, Chinese Academy of Sciences, Xu Weiqi, Research Group and State Key Laboratory of Molecular Biology, Li Boliang, Research Group, in a collaborative study It was found that "metabolism checkpoints" can regulate the anti-tumor activity of T cells, and identified a new target for tumor immunotherapy - cholesterol esterase ACAT1 and corresponding small molecule prodrugs, laying the foundation for the development of new tumor immunotherapy methods. The foundation. Today, the research results entitled "Enhanced anti-tumor response of CD8+ (plus is superscript) T cells by regulating cholesterol metabolism" were published online in the world's leading academic journal Nature.
The body's immune system is responsible for the health of the body, and T cells play a vital role in the monitoring and killing of tumors. However, tumor cells can inhibit the anti-tumor activity of T cells through various mechanisms, thereby evading the attack of the immune system. Clinically, tumors can be treated by increasing the activity of T cells. At present, T cell-based tumor immunotherapy has achieved great success and has broad application prospects. However, existing treatments are only effective for some patients and have certain side effects. Therefore, scientists need to develop new methods of tumor immunotherapy to improve the efficacy and benefit more patients.
Xu Yuqi's research team and Li Boliang's research team have studied the anti-tumor immune function of T cells from a new perspective. Researcher Xu Yiqi said that by regulating the "metabolism checkpoint" of T cells, the metabolic state can be changed to obtain a stronger anti-tumor effect. The researchers found that the cholesterol esterase ACAT1 in the T cell metabolic pathway is a good target for regulation. The inhibition of ACAT1 activity can greatly enhance the anti-tumor function of CD8+ T cells (also known as killer T cells). Because ACAT1 is inhibited, the level of free cholesterol on the killer T cell membrane is increased, making the T cell tumor antigen immune response more efficient. At the same time, the researchers also used ACAT1's small molecule inhibitor avasimibe to treat tumors in a mouse model and found that the inhibitor has a good anti-tumor effect; and avasimibe is associated with the existing tumor immunotherapy clinical drug anti-PD-1. The effect is better after use.
Wang Hongyang, an academician of the Chinese Academy of Engineering, commented on the research results: this is an important breakthrough in the basic research of tumor immunity, opening up a new field of research on tumor immunotherapy, demonstrating that cell metabolism plays a key role in tumor immune response, and discovers a new ACAT1. Drug targets reveal the application prospects of ACAT1 small molecule inhibitors, providing new ideas and new methods for tumor immunotherapy.
According to reports, the research was obtained by Liu Xiaolong, a researcher at the Biochemical and Cell Research Institute, Professor Liu Wanli from Tsinghua University, Professor Song Baoliang from Wuhan University, Professor Zhou Penghui from Sun Yat-sen University, Professor Sun Shaocong from the University of Texas Anderson Cancer Center, and Ta-YuanChang from Dartmouth Medical College. The professor's great help, and received funding support from the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chinese Academy of Sciences, and the Shanghai Science and Technology Commission, and the National Protein Science Research (Shanghai) facility compound laser microscope system, biochemical and cell animal Strong support for analytical technology platforms, cell analysis technology platforms, and molecular biology technology platforms.
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