On March 17, 2016, the international academic journal "nature" (nature) published online, Chinese Academy of Sciences, Shanghai Life Science Research Institute of Biochemistry and Cell Biology Research State Key Laboratory of Molecular Biology Institute / National Center for Protein Science (Shanghai) Xu Chenqi study group and molecular biology of State Key Laboratory of non research group cooperative research "by regulating cholesterol metabolism enhance CD8 + T cell antitumor responses" (Potentiating the antitumour response of CD8 + T cells by modulating cholesterol metabolis). The results found that "metabolic checkpoint" can the anti-tumor activity of regulatory T cells and the identification of new targets for cancer immunotherapy -- cholesterol esterifying enzyme ACAT1 and corresponding small molecule drug precursors and to develop new methods of tumor immunotherapy laid the foundation.
The body's immune system is responsible for the defense of the body's health, in which T cells play a critical role in tumor surveillance and killing. However, tumor cells can inhibit the anti-tumor activity of T cells by a variety of mechanisms, thus evading the immune system's attack. In clinic, it can be improved by increasing the activity of T cells to treat the tumor. At present, tumor immunotherapy based on T cells has achieved great success, and has broad application prospects. But the existing treatment is only effective for some patients, and it has some side effects. So scientists need to develop new cancer immune therapy to improve outcomes and benefit more patients.
Xu Chenqi research team and Li Boliang research team from a new perspective to study the anti tumor immune function of T cells. Scientific researchers believe that by regulating the T cell's metabolic checkpoint can change its metabolic state, so that it can get a stronger anti tumor effect. The researchers found that the cholesterol ester enzyme ACAT1 in T cell metabolism pathway is a good control target, which can greatly enhance the anti tumor function of CD8+T cells (also known as killer T cells), which can inhibit the ACAT1 activity. Because ACAT1 is inhibited, the killer T cell membrane free cholesterol levels increased, so that the T cell tumor antigen immune response has become more efficient. At the same time, researchers also use of ACAT1 small molecule inhibitors avasimibe in a mouse model in the treatment of tumor, found that the inhibitor has good anti-tumor effect; and avasimibe with existing tumor immune treatment of clinical drug anti-PD-1 combined effect is better. The study opens up a new field in the research of tumor immunotherapy that cell metabolism of tumor immune response to the key role, also found that ACAT1 this new drug targets, reveal the application prospect of ACAT1 small molecule inhibitors, provides new ideas and new methods for cancer immunotherapy.
The research is supported by the biochemical and cell researcher Liu Xiaolong, Tsinghua University Professor Liu, Wuhan University Professor Song Baoliang, Sun Yat sen University professor Zhou Penghui, the University of Texas MD Anderson Cancer Center, Professor Sun Shaocong and at Dartmouth Medical School professor Ta-Yuan Chang vigorously to help, and get the funding of National Natural Science foundation of commission, the State Ministry of science and technology, Chinese Academy of Sciences pilot projects and Shanghai Municipal Science and Technology Commission support. The research work also received national protein sciences (Shanghai) facilities composite laser microscope system, biochemical and cell animal analysis technology platform, the cell analysis platform technology and molecular biology technology platform support.