Regulation of PD-L1: a novel role of pro-survival signalling in cancer

Chen, J., Jiang, C. C., Jin, L. and Zhang, X. D. (2016) Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Annals of Oncology, 27 3: 409-416. doi:10.1093/annonc/mdv615

Author Chen, J.
Jiang, C. C.
Jin, L.
Zhang, X. D.
Title Regulation of PD-L1: a novel role of pro-survival signalling in cancer
Journal name Annals of Oncology   Check publisher's open access policy
ISSN 1569-8041
Publication date 2016-03-01
Year available 2015
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1093/annonc/mdv615
Open Access Status Not Open Access
Volume 27
Issue 3
Start page 409
End page 416
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 2720 Hematology
2730 Oncology
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.
Keyword Akt
Immune checkpoint
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published online 17 December 2015

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2016 Collection
School of Biomedical Sciences Publications
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