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

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. Inhibition of T cell activation by PD‐L1/PD‐1 signalling pathway. Binding of TCR/MHC signal 1 and CD28/B7 signal 2 activates T cell adaptive immune response. Binding of PD‐L1 and PD‐1 recruits SHP2 and leads to the dephosphorylation of ZAP‐70, CD3, and CD28, resulting in TCR signalling pathway abolition and inhibition of T cells activation and proliferation.