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. 2023 Mar 5;13(5):1520–1544. doi: 10.7150/thno.80091

Figure 5.

Figure 5

Schematic illustrations of strategies to enhance the efficacy of immunotherapy through degradation of PD-L1. (A) Schematic of the mechanism that metformin-activated AMPK phosphorylates PD-L1 at S195 to induce abnormal glycosylation and degrades PD-L1 through ERAD pathway. Reproduced from Ref 103. Copyright 2018, Cell Press. (B) PD-LYSO and HIP1R depleted PD-L1 through lysosomal degradation. Reproduced from Ref 110. Copyright 2022, Springer Nature. (C) Palmitoylation inhibitors facilitate PD-L1 ubiquitination and degradation. (D) Schematic of CPP-S1 and CPP-S2 peptides. The red highlights the differences between them. (E) Western blotting results of PD-L1 and GAPDH antibodies in RKO cells when incubated with CPPtat-S1 and CPPtat-S2 at different concentrations. (C), (D) and (E) were reproduced from Ref 44. Copyright 2022, Springer Nature. (F) Plasma membrane associated PD-L1 degradation through interruption of the electrostatic interaction between the polybasic residues and the acidic phospholipids. Reproduced form Ref 111. Copyright 2021, Springer Nature.