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- W2996085655 abstract "PD-L1 and PD-L2 are important targets for immune checkpoint blockade, but how tumor cells achieve their expression remains to be addressed. Here, we find that PD-L1 and PD-L2 are co-expressed in cancer cell lines and tissues across different cancer types. In breast cancer, MDA-MB-231 and SUM-159 cells show high expression of both PD-L1 and PD-L2. The expression of both PD-L1 and PD-L2 is greatly reduced upon treatment of inhibitors of super-enhancers. Bioinformatic analysis identifies a potential super-enhancer (PD-L1L2-SE) that is located between the CD274 and CD273 genes. Genetic deletion of PD-L1L2-SE profoundly reduces the expression of PD-L1 and PD-L2. PD-L1L2-SE-deficient cancer cells fail to generate immune evasion and are sensitive to T cell-mediated killing. Notably, epigenetic activation of such a region (PD-L1L2-SE) is correlated with PD-L1 and PD-L2. Taken together, we identify a super-enhancer (PD-L1L2-SE) that is responsible for the overexpression of PD-L1 and PD-L2 as well as immune evasion in cancer." @default.
- W2996085655 created "2019-12-26" @default.
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- W2996085655 date "2019-12-01" @default.
- W2996085655 modified "2023-10-18" @default.
- W2996085655 title "A Tumor-Specific Super-Enhancer Drives Immune Evasion by Guiding Synchronous Expression of PD-L1 and PD-L2" @default.
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- W2996085655 doi "https://doi.org/10.1016/j.celrep.2019.10.093" @default.
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