Table 1 Regulation of PD-L1 expression on the surface of tumor cells
Stage of regulation | Regulatory mechanism | PD-L1 level | References |
|---|---|---|---|
Genomic alternations | PD-L1 amplification and translocation in the genome | Up | |
Genomic alternations | Deletion of the 3'UTR of PD-L1 | Up | [60] |
Epigenetic regulations | Histone acetylation or methylation of H3K3me3 | Up | |
Transcriptional level | Upregulation of inflammatory cytokines (e.g., IFN- α/β, IFN-γ, TLR3/4, TNFα, TGFβ and IL-4/6/10/17/27) | Up | |
Transcriptional level | Aberrant oncogenic signaling pathways up regulate the expression of PD-L1(e.g., MYC, RAS, HIF1/2α, ALK, STAT3, EGFR, PI3K, MAPK) | Up | |
Post-transcriptional regulation | MiRNAs, including miR-34a, miR-200, miR-152, miR-217, miR-124-3p, and miR-383-5p, can downregulate the expression of PD-L1 | Down | |
Post-translational modification | Interaction between GSK3B and non-glycosylated PD-L1 | Down | [94] |
Post-translational modification | B3GNT3 promotes the N-glycosylation of PD-L1 | Up | [95] |
Post-translational modification | Tyr phosphorylation on PD-L1 through the IL-6/JAK1 pathway is necessary for the combination of PD-L1 and the N-glycosyltransferase STT3A to upregulate PD-L1 expression | Up | [96] |
Post-translational modification | CSN5 and the deubiquitinase USP22 inhibit PD-L1 ubiquitination and degradation | Up |