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

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

2024 | Te-An Lee12, En-Yun Tsai13, Shou-Hou Liu1, Shih-Duo Hsu Hung1, Shing-Jyh Chang4, Chi-Hong Chao5,6, Yun-Ju Lai7, Hirohito Yamaguchi8, and Chia-Wei Li1
The article "Post-translational Modification of PD-1: Potential Targets for Cancer Immunotherapy" by Te-An Lee et al. explores the role of post-translational modifications (PTMs) in regulating the stability, localization, and interprotein interactions of PD-1, a key protein in immune checkpoint pathways. PTMs such as glycosylation, phosphorylation, ubiquitination, and palmitoylation play crucial roles in modulating PD-1's function, which is essential for understanding and enhancing anti-tumor immunity. The authors highlight that targeting PTMs of PD-1 can overcome PD-1-mediated immunosuppression in cancer and improve the efficacy of anti-PD-1 therapies. They discuss the regulatory signaling pathways that induce PTMs of PD-1 and the potential therapeutic strategies, including small-molecule inhibitors and mAbs, to target these PTMs. The review also reviews the biological functions of PD-1 on different cell types, including immune cells and cancer cells, and the diverse roles of PD-1 in both inhibitory and activating immune responses. Additionally, the article provides an overview of the current state of PTM-based therapies, including glycosylation inhibitors, SHP-2 inhibitors, ERK inhibitors, and PROTACs, and their potential in cancer immunotherapy. The authors conclude by emphasizing the importance of further research to develop optimal therapeutic strategies targeting PTMs of PD-1.The article "Post-translational Modification of PD-1: Potential Targets for Cancer Immunotherapy" by Te-An Lee et al. explores the role of post-translational modifications (PTMs) in regulating the stability, localization, and interprotein interactions of PD-1, a key protein in immune checkpoint pathways. PTMs such as glycosylation, phosphorylation, ubiquitination, and palmitoylation play crucial roles in modulating PD-1's function, which is essential for understanding and enhancing anti-tumor immunity. The authors highlight that targeting PTMs of PD-1 can overcome PD-1-mediated immunosuppression in cancer and improve the efficacy of anti-PD-1 therapies. They discuss the regulatory signaling pathways that induce PTMs of PD-1 and the potential therapeutic strategies, including small-molecule inhibitors and mAbs, to target these PTMs. The review also reviews the biological functions of PD-1 on different cell types, including immune cells and cancer cells, and the diverse roles of PD-1 in both inhibitory and activating immune responses. Additionally, the article provides an overview of the current state of PTM-based therapies, including glycosylation inhibitors, SHP-2 inhibitors, ERK inhibitors, and PROTACs, and their potential in cancer immunotherapy. The authors conclude by emphasizing the importance of further research to develop optimal therapeutic strategies targeting PTMs of PD-1.
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[slides and audio] Post-translational Modification of PD-1%3A Potential Targets for Cancer Immunotherapy