Post-translational Modification of PD-1: Potential Pathways for Cancer Immunotherapy.

Activation of effector T cells leads to upregulation of PD-1, which can inhibit T cell activity following engagement with its ligand PD-L1. Post-translational modifications (PTMs), including glycosylation, phosphorylation, ubiquitination, and palmitoylation, play a significant role in regulating PD-1 protein stability, localization, and inter-protein interactions. Targeting PTM of PD-1 in T cells has emerged as a potential strategy to overcome PD-1-mediated immunosuppression in cancer and enhance antitumor immunity. The regulatory signaling pathways that induce PTM of PD-1 can be suppressed with small-molecule inhibitors, and monoclonal antibodies can directly target PD-1 PTMs. Preliminary outcomes from exploratory studies suggest that focusing on the PTM of PD-1 has strong therapeutic potential and can enhance the response to anti-PD-1.