Cis-interaction network of PD-L1 and its impact on anti-cancer immunotherapy
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Abstract:
In recent years, investigation on immune checkpoint inhibitors has made exciting progress in anti-tumor therapy. Through continuous exploration, there is a deeper understanding of intermolecular interaction patterns among PD-L1, PD-1, CD80, CTLA-4, etc.In addition to classically acting as a T cell inhibitory receptor, PD-L1 was found to be co-expressed with PD-1 or CD80 on the same cell and play a positive immunoregulatory function through cis-interaction, significantly affecting the interaction network between tumor cells and immune cells and the efficacy of immunotherapy, and bringing new changes to the understanding of the mechanisms of cancer immunotherapy. This review provides an in-depth analysis of the cis-PD-L1/PD-1 and cis-PD-L1/CD80 pathways and their interactions with a complex network of CTLA-4 and CD28 molecules, finally outlines the effects of blocking this cis-interaction pathway on T cell signaling, cytotoxic function, and the efficacy of anti-tumor immunotherapy.
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Project supported by the National Key R&D Program of China (No. 2016YFC1303800); the Science and Technology Development Project from Department of Science and Technology of Jilin Province (No. 20190303146SF); the Special Project for Provincial Industrial Innovation of Development and Reform Commission in Jilin Province (No. 2017C022), and the Key Laboratory Construction Project of Department of Science and Technology of Jilin Province (No. 20170622011JC)