In the endoplasmic reticulum (ER), PD-1 is glycosylated at residues N49 and N74, and its subsequent fucosylation (red triangle) in the Golgi leads to sustained expression and transmission of PD-1 at the cell membrane, reducing PD-1 glycosylation, expression, and inhibitory signaling, resulting in increased T cell activation. The FBXO 38 ubiquitin ligase mediates the ubiquitination of the K48 ligation of PD-1 at K233, leading to PD-1 internalization and proteasomal degradation. Gene elimination or down of FBXO 38 results in increased PD-1 expression, resulting in inhibitory signaling and enhanced T cell suppression. PD-L1 expression in tumor cells is stabilized by glycosylation. This is antagonized by GSK 3 β, where GSK 3 β binds to the unglycosylated form of PD-L1, leading to phosphorylation at T180 and S184, as well as β -TrCP-mediated ubiquitination and proteasome degradation of PD-L1. EGFR-mediated signaling suppresses GSK 3 β --mediated PD-L1 phosphorylation and degradation and promotes PD-L1 stabilization and immunosuppressive functions. An antibody targeting glycated PD-L1 (anti-gPD-L1) blocks the interaction with PD-1 and induces PD-L1 internalization and degradation. In cancer cells, TNFR-mediated signaling leads to IKK-mediated p65 activation and nuclear translocation, leading to CSN 5 transcription, and CSN 5 stabilizes PD-L1 by direct deubiquitination or inhibiting PD-L1 ubiquitination, thereby enhancing immunosuppressive activity.