PD-1/PD-L1 immune checkpoint blockade therapy has become an effective method for the treatment of cancers in the clinic. It has great clinical advantages and therapeutic effects in the treatment of various cancers. However, a considerable number of cancer patients currently have relatively low response rates and drug resistance to PD-1/PD-L1 immunotherapy. Therefore, an in-depth understanding of the regulatory mechanism of PD-L1 expression in tumor cells will provide new insights into PD-1/PD-L1 immunotherapy. This review will systematically review the regulatory mechanisms of PD-L1 including genomic amplification, epigenetic regulation, transcriptional regulation, translational regulation and posttranslational modification. We will also discuss PD-L1 expression regulation in clinical applications. Finally, we hope to provide new routes for PD-1/PD-L1 immunotherapy in the clinic.
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