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

Cancer Res. 2018 Nov 15;78(22):6349-6353. doi: 10.1158/0008-5472.CAN-18-1892.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Animals
  • Antineoplastic Agents / pharmacology
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Dendrites / metabolism
  • Endoplasmic Reticulum / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Glycosylation
  • Humans
  • Immunotherapy
  • Inflammation
  • Ligands
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Processing, Post-Translational*
  • Protein Stability
  • Signal Transduction
  • Ubiquitination


  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • Cytokines
  • Ligands
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease