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    Home > Active Ingredient News > Immunology News > Immunity . . . The Whine group clarified the conjugate relationship between tumor immunotherapy targets.

    Immunity . . . The Whine group clarified the conjugate relationship between tumor immunotherapy targets.

    • Last Update: 2020-07-23
    • Source: Internet
    • Author: User
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    The immune system, especially T cells, has the ability to recognize and attack tumor cells. However, tumor cells will use various mechanisms to escape the attack of the immune system: for example, tumor cells express the ligand protein PD-L1 on the surface of tumor cells, and antagonize the antitumor activity of T cells by binding PD-L1 to the inhibitory receptor PD-1 on T cells.this mechanism is like a tumor stepping on the brake of T cells, resulting in T cells unable to be normally activated and attack the tumor.in addition to PD-1, there are other inhibitory receptors (brakes) on T cells, such as CTLA-4.at present, a very effective cancer immunotherapy is to block the binding of PD-1 and PD-L1 with monoclonal antibodies, or to block CTLA-4, so as to prevent tumor cells from inhibiting T cells.James Allison and Tasuku Honjo won the 2018 Nobel Prize in physiology and medicine for their pioneering work in cancer immunotherapy.unfortunately, blocking antibodies against PD-1, PD-L1 or CTLA-4 are effective only in a few tumors and a few patients, and the reason is unknown.scientists also found that blocking both PD-1 / PD-L1 and CTLA-4 is better than blocking one pathway alone, but the underlying mechanism is still unclear.on November 19, 2019, the team of Enfu Hui of the University of California, San Diego (UCSD) published a long article "PD-L1: CD80 CIS heterodimer triggers the co stitution receptor CD28 while expressing the inhibitor PD-1 and CTLA-4 Pathways "reveals an unexpected conjugation between PD-1 and CTLA-4 pathways, and explains why blocking PD-L1 and CTLA-4 at the same time can more effectively activate the anti-tumor immunity of T cells. Br / > the PD < 1protein is generally considered to be an immunosuppressive ligand for PD. CD80 is not only a ligand for CTLA-4, but also a co stimulatory receptor (CD28) on T cells.using a series of ingenious biochemical and cell biological methods, the authors have proved that PD-L1 and CD80 can form heterodimer by CIS interaction in the same cell.interestingly, this PD-L1: CD80 heterodimer blocked both PD-1 and CTLA-4 pathways, but activated CD28.this study revealed that PD-L1 not only has a well-known immunosuppressive function, but also has an immune activation effect - it can significantly weaken the function of CTLA-4 by CIS binding with CD80.the authors further demonstrated that atezolizumab, an anti-PD-L1 blocking antibody approved by FDA, not only blocked the binding of PD-L1 and PD-1, but also blocked the CIS binding of PD-L1 and CD80, resulting in the dissociation of PD-L1: CD80 heterodimer.after being dissociated by atezolizumab, CD80 can better bind and activate CTLA-4 inhibitory pathway, which leads to the decrease of T cell activity.these results reveal an unknown side effect of PD-L1 blocking antibody: activation of CTLA-4 pathway.therefore, the drug releases one brake (PD-1) and enhances the other brake (CTLA-4). it is worth mentioning that the side effect of blocking antibody of PD-L1 can be effectively prevented by adding CTLA-4 blocking antibody ipilimumab on the basis of atezolizumab. in conclusion, this new study reveals for the first time the conjugation mechanism of PD-1 and CTLA-4 T cell braking: through CIS interaction, CD80, a ligand of CTLA-4, can block the interaction between PD-L1 and PD-1, and PD-L1 can weaken the interaction between CD80 and CTLA-4. this conjugate relationship provides a theoretical and practical basis for the combination therapy of PD-L1 and CTLA-4. Dr. Yunlong Zhao of the University of California is the first author of this paper, and Dr. huinfu is the corresponding author. collaborators include Jack bui and Li Fan Lu from the University of California, Cristina bonorino from Brazil, and Changchun Xiao from Scripps Institute. original link:
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