Author: Shen then Jin Release Date: 2019-02-25
Not long ago, the world's leading academic journal Nature published the research results of the research team of the National Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences ("Chinese Academy of Sciences Biochemistry and Cell Research"). This research reveals for the first time the degradation mechanism of PD-1, a "brake" molecule in the human immune system, and its function in tumor immune response.
As a part of the human immune system, T cells are important "guardians" of the body's health, which can identify and eliminate mutant cells in vivo to prevent tumors. However, some tumor cells will "brake" the immune system by activating PD-1 molecules, thereby avoiding T cell killing. Clinically, antibody drugs that block the PD-1 pathway can restore the patient's own anti-tumor immune function, thereby treating the tumor. At present, these drugs have achieved great success and can treat more than 10 kinds of tumors such as lung cancer, liver cancer and kidney cancer. The discoverers of PD-1 also received the 2018 Nobel Prize in Physiology or Medicine. However, why is PD-1 so "active" in the tumor microenvironment? This important scientific issue is still not well explained.
Xu Yiqi's team has long been committed to the functional regulation of T cells. It has discovered the activation mechanism of key receptors in T cells and the regulation of cholesterol metabolism on T cells. In this study, they studied the regulation mechanism of PD-1 from a new perspective and found that PD-1 has a rapid degradation process in normal T cells, and identified the key protein FBXO38. FBXO38 can add a label that mediates degradation to PD-1, and PD-1 will be sent to the cell recovery site, the proteasome for degradation, to ensure that PD-1 maintains normal levels and does not affect T cells. Features. However, in T cells "surrounded" by tumors, FBXO38 is "active" to a low level, which may result in PD-1 not being normally degraded. Therefore, T cells are "trapped" by PD-1, which should be degraded, and the anti-tumor immune response is inhibited.
Through further research, Xu Yiqi's team found that interleukin 2 can restore the "active" degree of FBXO38, allowing PD-1 to return to the "normal index", thereby improving the anti-tumor function of T cells. Interleukin 2 is a clinical drug for the treatment of melanoma and renal cancer, and its regulation of PD-1 should be one of the mechanisms behind its clinical effects. It should be pointed out that due to the large side effects, interleukin 2 has not been widely used in clinical practice. In this regard, in the future, it is possible to optimize its dosage form and dosage, and explore its prospects for combination therapy with other drugs.
The study sheds light on the new regulatory mechanisms of PD-1, an important drug target, which helps researchers better understand tumor immune responses and design new methods for tumor immunotherapy.
Source: China Economic Net
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