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

Overview

Journal Cancer Res

Specialty Oncology

Date 2024 Jan 17

PMID 38231470

Authors

Te-An Lee

En-Yun Tsai

Shou-Hou Liu

Shih-Duo Hsu Hung

Shing-Jyh Chang

Chi-Hong Chao

Yun-Ju Lai

Hirohito Yamaguchi

Chia-Wei Li

Affiliations

Soon will be listed here.

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.

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