4.6 Review

Anti-tumour potential of PD-L1/PD-1 post-translational modifications

Journal

IMMUNOLOGY
Volume 167, Issue 4, Pages 471-481

Publisher

WILEY
DOI: 10.1111/imm.13573

Keywords

cancer research; drug development; PD-1; PD-L1; post-translational modification; tumour immunotherapy

Categories

Funding

  1. National Natural Science Foundation of China [82030077, 8192913]
  2. Natural Science Foundation of Jiangsu Province [BK20190821]
  3. China Postdoctoral Science Foundation [2019 M651953, 2021 T140496]
  4. Jiangsu Postdoctoral Research Foundation [2021K627C]
  5. Open Project Program of the State Key Laboratory of Radiation Medicine and Protection [GZK1201909]
  6. Priority Academic Program Development of Jiangsu Higher Education Institutions

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The PD-L1/PD-1 signaling pathway is considered one of the main mechanisms of tumor escape from immune surveillance. PD-L1 is highly expressed on tumor cells and binds to the PD-1 receptor on activated T cells, inhibiting their anti-tumor activity. Recent research has focused on post-translational modifications of PD-L1/PD-1, such as glycosylation, ubiquitination, phosphorylation, and acetylation, and their potential role in regulating the signaling pathway and anti-tumor function of T cells.
The immune checkpoint programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) are biologically important immunosuppressive molecules, and the PD-L1/PD-1-mediated signalling pathway is currently considered one of the main mechanisms of tumour escape immune surveillance. PD-L1 is highly expressed on the cytomembrane of tumour cell and binds to PD-1 receptor of activated T cells. This interaction activates PD-L1/PD-1 downstream signal transduction, inhibiting T cells anti-tumour activity. Therefore, inhibitors of PD-L1/PD-1 activation, showing significant efficacy in some types of tumours, have been widely approved in clinical tumour therapy. Recent research on PD-L1/PD-1 signalling pathway regulation has shown post-translational modifications (PTMs) form of PD-L1 or PD-1, including glycosylation, ubiquitination, phosphorylation, and acetylation, which may play an important role in PD-L1/PD-1 signalling pathway regulation and anti-tumour function of T cells. In this review, we focused on PTMs of PD-L1/PD-1 research and potential applications in tumour immunotherapy.

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