Acetylation

SUMO protein

Glycosylation

Effector

Biology

Gene

Cancer

Ubiquitin ligase

Phosphorylation

Chemistry

Immunology

Ubiquitin

Neddylation

Cell biology

Cancer research

Genetics

Biochemistry

Immune system

Cancer cell

Cancer Research

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.

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