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


ABSTRACT: 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.

SUBMITTER: Lee TA 

PROVIDER: S-EPMC10940856 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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

Lee Te-An TA   Tsai En-Yun EY   Liu Shou-Hou SH   Hsu Hung Shih-Duo SD   Chang Shing-Jyh SJ   Chao Chi-Hong CH   Lai Yun-Ju YJ   Yamaguchi Hirohito H   Li Chia-Wei CW  

Cancer research 20240301 6


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  ...[more]

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