Regulation of PD-L1 expression in cancer and clinical implications in immunotherapy

Abstract

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.

Keywords: Immune checkpoint blockade therapy; PD-1/PD-L1; gene expression; regulatory mechanism.

Figure 1

Classification of PD-L1 expression. PD-L1 expression can be divided into constitutive expression and inducible expression. Constitutive expression is induced by dysregulation of signal transduction components in tumor cells. Inducible expression is induced by a number of inflammatory cytokines.

Figure 2

Regulation of PD-L1 expression in cancer cells at different levels. PD-L1 expression can be regulated by genomic amplification, transcriptional regulation, epigenetic regulation and transcriptional regulation.