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Posttranslational Modifications of PD-L1 and Their Applications in Cancer Therapy.


ABSTRACT: 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 promising antitumor effects and that clinical translation of these therapeutic strategies is warranted. Cancer Res; 78(22); 6349-53. ©2018 AACR.

SUBMITTER: Hsu JM 

PROVIDER: S-EPMC6242346 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Posttranslational Modifications of PD-L1 and Their Applications in Cancer Therapy.

Hsu Jung-Mao JM   Li Chia-Wei CW   Lai Yun-Ju YJ   Hung Mien-Chie MC  

Cancer research 20181101 22


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 regulat  ...[more]

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