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Abstract
Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape
the attack from immune cells. Cancer cells can express many immune inhibitory signalling
proteins to cause immune cell dysfunction and apoptosis. One of these inhibitory molecules
is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed
on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer
immunity. Therefore, anti-PD-L1 and anti-PD-1 antibodies have been used for the treatment
of cancer, showing promising outcomes. However, only a proportion of patients respond
to the treatments. Further understanding of the regulation of PD-L1 expression could
be helpful for the improvement of anti-PD-L1 and anti-PD-1 treatments. Studies have
shown that PD-L1 expression is regulated by signalling pathways, transcriptional factors
and epigenetic factors. In this review, we summarise the recent progress of the regulation
of PD-L1 expression in cancer cells and propose a regulatory model for unified explanation.
Both PI3K and MAPK pathways are involved in PD-L1 regulation but the downstream molecules
that control PD-L1 and cell proliferation may differ. Transcriptional factors hypoxia-inducible
factor-1α and signal transducer and activation of transcription-3 act on the promoter
of PD-L1 to regulate its expression. In addition, microRNAs including miR-570, miR-513,
miR-197, miR-34a and miR-200 negatively regulate PD-L1. Clinically, it could increase
treatment efficacy of targeted therapy by choosing those molecules that control both
PD-L1 expression and cell proliferation.