Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies
Abstract Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have revolutionized cancer clinical management, but low response rates and treatment resistance remain challenging. Protein post-translational modifications (PTMs) are critical for governing protein expression, localization,...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-025-02397-5 |
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| author | Haiqing Jia Lei Jiang Xiaoyu Shen Huinan Ye Xinguang Li Liwei Zhang Yanyan Hu Dandan Song Hui Jia Zhe Wang |
| author_facet | Haiqing Jia Lei Jiang Xiaoyu Shen Huinan Ye Xinguang Li Liwei Zhang Yanyan Hu Dandan Song Hui Jia Zhe Wang |
| author_sort | Haiqing Jia |
| collection | DOAJ |
| description | Abstract Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have revolutionized cancer clinical management, but low response rates and treatment resistance remain challenging. Protein post-translational modifications (PTMs) are critical for governing protein expression, localization, functions, and interactions with other cellular molecules, which notably build up the diversity and complexity of the proteome. A growing body of evidence supports that PTMs influence immunotherapy efficacy and outcomes by post-translationally modulating the expression and functions of immune checkpoints. Therefore, understanding the PTM mechanisms that govern immune checkpoints is paramount for developing novel treatment strategies to improve immunotherapy efficacy and overcome resistance. This review provides an overview of the current comprehension of the regulatory mechanisms by which PTMs (glycosylation, phosphorylation, ubiquitination, acetylation, succinylation, palmitoylation, lactylation, O-GlcNAcylation, UFMylation, and neddylation) modulate immune checkpoints to unveil potential therapeutic targets. Moreover, this review discusses the potential of therapeutic strategies targeting PTMs of immune checkpoints, providing insights into the combination treatment with ICIs in maximizing the benefits of immunotherapy and overcoming resistance. |
| format | Article |
| id | doaj-art-f47500b84b0444f7bf7b18f249dae929 |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-f47500b84b0444f7bf7b18f249dae9292025-08-20T03:45:48ZengBMCMolecular Cancer1476-45982025-07-0124113510.1186/s12943-025-02397-5Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategiesHaiqing Jia0Lei Jiang1Xiaoyu Shen2Huinan Ye3Xinguang Li4Liwei Zhang5Yanyan Hu6Dandan Song7Hui Jia8Zhe Wang9Department of Gynecology Surgery 1, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteDepartment of Breast Medicine 1, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteDepartment of Thoracic Medicine 2, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteDepartment of Digestive Diseases 1, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteDepartment of General Surgery, Fuxin Central HospitalDepartment of Vascular Interventional Therapy, General Hospital of Northern Theater CommandDepartment of Digestive Diseases 1, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteDepartment of Respiratory and Critical Care Medicine, The First Hospital of China Medical UniversityDepartment of Anesthesiology, The First Hospital of China Medical UniversityDepartment of Digestive Diseases 1, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & InstituteAbstract Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have revolutionized cancer clinical management, but low response rates and treatment resistance remain challenging. Protein post-translational modifications (PTMs) are critical for governing protein expression, localization, functions, and interactions with other cellular molecules, which notably build up the diversity and complexity of the proteome. A growing body of evidence supports that PTMs influence immunotherapy efficacy and outcomes by post-translationally modulating the expression and functions of immune checkpoints. Therefore, understanding the PTM mechanisms that govern immune checkpoints is paramount for developing novel treatment strategies to improve immunotherapy efficacy and overcome resistance. This review provides an overview of the current comprehension of the regulatory mechanisms by which PTMs (glycosylation, phosphorylation, ubiquitination, acetylation, succinylation, palmitoylation, lactylation, O-GlcNAcylation, UFMylation, and neddylation) modulate immune checkpoints to unveil potential therapeutic targets. Moreover, this review discusses the potential of therapeutic strategies targeting PTMs of immune checkpoints, providing insights into the combination treatment with ICIs in maximizing the benefits of immunotherapy and overcoming resistance.https://doi.org/10.1186/s12943-025-02397-5Immune checkpointsPost-translational modificationsImmunotherapyTreatment resistanceCombination treatment |
| spellingShingle | Haiqing Jia Lei Jiang Xiaoyu Shen Huinan Ye Xinguang Li Liwei Zhang Yanyan Hu Dandan Song Hui Jia Zhe Wang Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies Molecular Cancer Immune checkpoints Post-translational modifications Immunotherapy Treatment resistance Combination treatment |
| title | Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies |
| title_full | Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies |
| title_fullStr | Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies |
| title_full_unstemmed | Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies |
| title_short | Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies |
| title_sort | post translational modifications of cancer immune checkpoints mechanisms and therapeutic strategies |
| topic | Immune checkpoints Post-translational modifications Immunotherapy Treatment resistance Combination treatment |
| url | https://doi.org/10.1186/s12943-025-02397-5 |
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