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- W4220808297 abstract "CTLA-4 and PD-1 are key immune checkpoints that are targeted in the treatment of cancer. Recently it has emerged that there is a physical interaction between the ligands of these pathways (CD80 and PD-L1), which can prevent PD-L1 inhibitory functions. Since CTLA-4 captures and degrades its ligands via transendocytosis, we investigated how transendocytosis of CD80 is impacted by PD-L1 interaction. We find that transendocytosis of CD80 results in a time-dependent recovery of PD-L1 availability that correlates with CD80 removal. Moreover, CD80 transendocytosis is highly specific in that only CD80 is removed, and its heterodimeric PD-L1 partner remains on the APC. We found no evidence that CTLA-4 interactions with CD80 were inhibited by PD-L1, however efficient removal of CD80 required an intact CTLA-4 cytoplasmic domain, distinguishing this process from more general trogocytosis. We also show that simple binding of CTLA-4 to the CD80-PD-L1 heterodimer is insufficient to liberate PD-L1-PD-1 interactions, suggesting that transendocytosis of CD80 is required to effectively control PD-L1-PD-1 interactions." @default.
- W4220808297 created "2022-04-03" @default.
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- W4220808297 date "2022-03-28" @default.
- W4220808297 modified "2023-09-23" @default.
- W4220808297 title "CTLA-4 regulates PD-L1-PD-1 interactions via transendocytosis of CD80" @default.
- W4220808297 doi "https://doi.org/10.1101/2022.03.28.486104" @default.
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