Regulation of post-translational modification of PD-L1 and advances in tumor immunotherapy

Frontiers in Immunology

Immunology

Tao Zhang¹  Xin Chang²  Dongliang Qin³  Lening Zhang³  Chong Feng³ 

[1] Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China;Ophthalmology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China;Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China;

关键词: post-translational modification;    tumor immunotherapy;    programmed death ligand 1;    glycosylation;    ubiquitination;    phosphorylation;    acetylation;    S-palmitoylation;   

DOI  :  10.3389/fimmu.2023.1230135

 received in 2023-05-28, accepted in 2023-07-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

The immune checkpoint molecules programmed cell death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) are one of the most promising targets for tumor immunotherapy. PD-L1 is overexpressed on the surface of tumor cells and inhibits T cell activation upon binding to PD⁃1 on the surface of T cells, resulting in tumor immune escape. The therapeutic strategy of targeting PD-1/PD-L1 involves blocking this binding and restoring the tumor-killing effect of immune cells. However, in clinical settings, a relatively low proportion of cancer patients have responded well to PD-1/PD-L1 blockade, and clinical outcomes have reached a bottleneck and no substantial progress has been made. In recent years, PD-L1 post-translation modifications (PTMs) have gradually become a hot topic in the field of PD-L1 research, which will provide new insights to improve the efficacy of current anti-PD-1/PD-L1 therapies. Here, we summarized and discussed multiple PTMs of PD-L1, including glycosylation, ubiquitination, phosphorylation, acetylation and palmitoylation, with a major emphasis on mechanism-based therapeutic strategies (including relevant enzymes and targets that are already in clinical use and that may become drugs in the future). We also summarized the latest research progress of PTMs of PD-L1/PD-1 in regulating immunotherapy. The review provided novel strategies and directions for tumor immunotherapy research based on the PTMs of PD-L1/PD-1.

【 授权许可】

Unknown   
Copyright © 2023 Feng, Zhang, Chang, Qin and Zhang