The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy
The tumor microenvironment (TME) is the tumor surrounding environment, which is critical for tumor development and progression. TME is also involved in clinical intervention and treatment outcomes. Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts w...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1123244/full |
| _version_ | 1797951451610218496 |
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| author | Bo Hou Ting Chen He Zhang Jiatong Li Peter Wang Guanning Shang |
| author_facet | Bo Hou Ting Chen He Zhang Jiatong Li Peter Wang Guanning Shang |
| author_sort | Bo Hou |
| collection | DOAJ |
| description | The tumor microenvironment (TME) is the tumor surrounding environment, which is critical for tumor development and progression. TME is also involved in clinical intervention and treatment outcomes. Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts with PD-1 protein on T cells, contributing to T cell dysfunction and exhaustion, blockage of the immune response. Evidence has demonstrated that the expression of PD-1/PD-L1 is associated with clinical response to anti-PD-1/PD-L1 therapy in cancer patients. It is important to discuss the regulatory machinery how PD-1/PD-L1 protein is finely regulated in tumor cells. In recent years, studies have demonstrated that PD-1/PD-L1 expression was governed by various E3 ubiquitin ligases in TME, contributing to resistance of anti-PD-1/PD-L1 therapy in human cancers. In this review, we will discuss the role and molecular mechanisms of E3 ligases-mediated regulation of PD-1 and PD-L1 in TME. Moreover, we will describe how E3 ligases-involved PD-1/PD-L1 regulation alters anti-PD-1/PD-L1 efficacy. Altogether, targeting E3 ubiquitin ligases to control the PD-1/PD-L1 protein levels could be a potential strategy to potentiate immunotherapeutic effects in cancer patients. |
| first_indexed | 2024-04-10T22:30:47Z |
| format | Article |
| id | doaj.art-7790e0cce26f47e6aedda463c2084f8a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T22:30:47Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7790e0cce26f47e6aedda463c2084f8a2023-01-17T05:17:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.11232441123244The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapyBo Hou0Ting Chen1He Zhang2Jiatong Li3Peter Wang4Guanning Shang5Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui, ChinaDepartment of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaThe tumor microenvironment (TME) is the tumor surrounding environment, which is critical for tumor development and progression. TME is also involved in clinical intervention and treatment outcomes. Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts with PD-1 protein on T cells, contributing to T cell dysfunction and exhaustion, blockage of the immune response. Evidence has demonstrated that the expression of PD-1/PD-L1 is associated with clinical response to anti-PD-1/PD-L1 therapy in cancer patients. It is important to discuss the regulatory machinery how PD-1/PD-L1 protein is finely regulated in tumor cells. In recent years, studies have demonstrated that PD-1/PD-L1 expression was governed by various E3 ubiquitin ligases in TME, contributing to resistance of anti-PD-1/PD-L1 therapy in human cancers. In this review, we will discuss the role and molecular mechanisms of E3 ligases-mediated regulation of PD-1 and PD-L1 in TME. Moreover, we will describe how E3 ligases-involved PD-1/PD-L1 regulation alters anti-PD-1/PD-L1 efficacy. Altogether, targeting E3 ubiquitin ligases to control the PD-1/PD-L1 protein levels could be a potential strategy to potentiate immunotherapeutic effects in cancer patients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1123244/fullE3 ligasescancertherapyPD-1PD-L1TME |
| spellingShingle | Bo Hou Ting Chen He Zhang Jiatong Li Peter Wang Guanning Shang The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy Frontiers in Immunology E3 ligases cancer therapy PD-1 PD-L1 TME |
| title | The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy |
| title_full | The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy |
| title_fullStr | The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy |
| title_full_unstemmed | The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy |
| title_short | The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy |
| title_sort | e3 ubiquitin ligases regulate pd 1 pd l1 protein levels in tumor microenvironment to improve immunotherapy |
| topic | E3 ligases cancer therapy PD-1 PD-L1 TME |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1123244/full |
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