TY - JOUR
T1 - Posttranslational modifications of PD-L1 and their applications in cancer therapy
AU - Hsu, Jung Mao
AU - Li, Chia Wei
AU - Lai, Yun Ju
AU - Hung, Mien Chie
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/11/15
Y1 - 2018/11/15
N2 - Posttranslational modifications (PTM) of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In exposure to inflammatory cytokines, cancer cells and antigen-presenting cells, such as macrophages and dendritic cells, express PD-L1 to inhibit the activity of effector T cells through PD-1 engagement. Recent studies suggested that glycosylation, phosphorylation, ubiquitination, sumoylation, and acetylation play important roles in the regulation of PD-L1 protein stability and translocation and protein–protein interactions. Aberrant alterations of PTMs directly influence PD-L1–mediated immune resistance. On the basis of the newly identified regulatory signaling pathways of PD-L1 PTMs, researchers have investigated the cancer therapeutic potential of natural food compounds, small-molecule inhibitors, and mAbs by targeting PD-L1 PTMs. Results of these preclinical studies demonstrated that targeting PTMs of PD-L1 yields promisin antitumor effects and that clinical translation of these therapeutic strategies is warranted.
AB - Posttranslational modifications (PTM) of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In exposure to inflammatory cytokines, cancer cells and antigen-presenting cells, such as macrophages and dendritic cells, express PD-L1 to inhibit the activity of effector T cells through PD-1 engagement. Recent studies suggested that glycosylation, phosphorylation, ubiquitination, sumoylation, and acetylation play important roles in the regulation of PD-L1 protein stability and translocation and protein–protein interactions. Aberrant alterations of PTMs directly influence PD-L1–mediated immune resistance. On the basis of the newly identified regulatory signaling pathways of PD-L1 PTMs, researchers have investigated the cancer therapeutic potential of natural food compounds, small-molecule inhibitors, and mAbs by targeting PD-L1 PTMs. Results of these preclinical studies demonstrated that targeting PTMs of PD-L1 yields promisin antitumor effects and that clinical translation of these therapeutic strategies is warranted.
UR - http://www.scopus.com/inward/record.url?scp=85056582164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056582164&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-18-1892
DO - 10.1158/0008-5472.CAN-18-1892
M3 - Article
C2 - 30442814
AN - SCOPUS:85056582164
SN - 0008-5472
VL - 78
SP - 6349
EP - 6353
JO - Cancer Research
JF - Cancer Research
IS - 22
ER -