biostudies-literatureUnknown84(6)Lee TAActivation 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 (PTM), including glycosylation, phosphorylation, ubiquitination, and palmitoylation, play a significant role in regulating PD-1 protein stability, localization, and interprotein interactions. Targeting PTM of PD-1 in T cells has emerged as a potential strategy to overcome PD-1-mediated immunosuppression in cancer and enhances antitumor immunity. The regulatory signaling pathways that induce PTM of PD-1 can be suppressed with small-molecule inhibitors, and mAbs 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.Cancer research800-807https://www.ebi.ac.uk/biostudies/studies/S-EPMC10940856biostudies-literaturePost-translational Modification of PD-1: Potential Targets for Cancer Immunotherapy.PMC10940856Liu SHChao CHTsai EYHsu Hung SDChang SJLi CWLai YJYamaguchi HLee TAfalsePost-translational Modification of PD-1: Potential Targets 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 (PTM), including glycosylation, phosphorylation, ubiquitination, and palmitoylation, play a significant role in regulating PD-1 protein stability, localization, and interprotein interactions. Targeting PTM of PD-1 in T cells has emerged as a potential strategy to overcome PD-1-mediated immunosuppression in cancer and enhances antitumor immunity. The regulatory signaling pathways that induce PTM of PD-1 can be suppressed with small-molecule inhibitors, and mAbs 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-1.2024-01-01T00:00:00Z2024 Mar2025-04-05T12:06:18.293Z2025-04-05T12:06:18.293ZS-EPMC109408563823147010.1158/0008-5472.CAN-23-2664