Tumor defense system can be disintegrated from the inside
November 20, 2018 Source: Health News
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)];Recently, a study by Xu Jie, a team of the Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, revealed the regulatory mechanism of tumor immunotherapy target programmed death ligand-1 (PD-L1), which is expected to more completely disintegrate tumor cells. defense. The related results paper was published recently in the journal Nature and Chemical Biology.
Xu Jie made a metaphor, PD-L1 protein can protect tumor cells from evading the killing of immune cells, just like the guards of the castle. A previous approach was to eliminate PD-L1 from the outside of the cell with antibodies, but PD-L1 would also replenish it to form resistance again. The new method uses a function called Huntington's Interacting Protein 1-related protein (HIP1R) to degrade PD-L1 from inside the cell, just like the "Trojan horse" that attacks the guard from inside the castle.
According to reports, tumor immunological checkpoint blockers such as anti-programmed death-1 (PD-1) receptor and its programmed death ligand (PD-L1) antibody drugs, mainly by overcoming the immunosuppression in patients, Reactivate the patient's own immune cells to kill the tumor.
Currently, PD-1 antibody drugs have been approved for marketing in the US and China. However, PD-1 inhibitors are only 10% to 30% effective in patients with unselected solid tumors, and drugs that are initially effective may also develop resistance. Recent studies have found that PD-L1 in tumor cells is also present in circulating endosomes, Golgi and microvesicles in cells. PD-L1 in cancer cells has a cancer-promoting function, which complements and renews the cell surface-inactivated PD-L1, which may be one of the causes of antibody drug failure.
Xu Jie's group found a significant association between PD-L1 and HIP1R through tumor genomics screening, and demonstrated that HIP1R promotes the degradation of PD-L1 from the lysosomal pathway, which is the “recycling station†that transports PD-L1 protein into cells. "To carry out a thorough removal. After losing the protection of PD-L1, the tumor cells will be killed by T cells in the body. The researchers designed a peptide based on HIP1R regulation of PD-L1, which can target PD-L1 to lysosomal degradation and promote the killing of tumor cells by immune cells.
Experts say the study provides new ideas and methods for tumor immunotherapy. The author of the paper is Xu Jie, the first author is Wang Huanbin, a doctoral student at Shanghai Jiao Tong University School of Medicine.
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