Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications
Summary: Immune checkpoint therapy targeting PD-L1/PD-1 represents a key cancer treatment strategy. PD-L1 binds PD-1 on T cells, suppressing activation and enabling tumor immune escape. Although the blockade of the PD-L1/PD-1 pathway has demonstrated significant anti-tumor effects, the overall respo...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225008764 |
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| author | Yifei Zhang Keyu Yin Runsheng Ma Yuxiao Sun Longlong Wang Detao Yin |
| author_facet | Yifei Zhang Keyu Yin Runsheng Ma Yuxiao Sun Longlong Wang Detao Yin |
| author_sort | Yifei Zhang |
| collection | DOAJ |
| description | Summary: Immune checkpoint therapy targeting PD-L1/PD-1 represents a key cancer treatment strategy. PD-L1 binds PD-1 on T cells, suppressing activation and enabling tumor immune escape. Although the blockade of the PD-L1/PD-1 pathway has demonstrated significant anti-tumor effects, the overall response rate remains suboptimal in solid tumors. Therefore, understanding the molecular mechanisms underlying PD-L1 deregulation is essential for enhancing the efficacy of PD-L1/PD-1 blockade therapies. As our comprehension of the regulatory mechanisms governing the PD-L1/PD-1 pathway continues to evolve, ongoing exploration of new immunotherapy targets remains critical. This article provides a comprehensive review of recent research concerning the regulation of PD-L1 expression. It encompasses aspects such as its structural characteristics, genomic alterations and rearrangements, epigenetic modifications, inflammatory signaling pathways, oncogenic signaling pathways, microRNA regulation, and post-translational modifications. Additionally, this article illustrates notable advancements and limitations regarding the application of PD-L1 as an immunotherapeutic target in current clinical settings. |
| format | Article |
| id | doaj-art-d914871ee2114b0e9ea6093d7be8ec1e |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-d914871ee2114b0e9ea6093d7be8ec1e2025-08-20T02:26:10ZengElsevieriScience2589-00422025-06-0128611261510.1016/j.isci.2025.112615Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applicationsYifei Zhang0Keyu Yin1Runsheng Ma2Yuxiao Sun3Longlong Wang4Detao Yin5Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Human Anatomy, College of Basic Medical Sciences, Lanzhou University, Gansu, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Zhengzhou, China; Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou, China; Corresponding authorSummary: Immune checkpoint therapy targeting PD-L1/PD-1 represents a key cancer treatment strategy. PD-L1 binds PD-1 on T cells, suppressing activation and enabling tumor immune escape. Although the blockade of the PD-L1/PD-1 pathway has demonstrated significant anti-tumor effects, the overall response rate remains suboptimal in solid tumors. Therefore, understanding the molecular mechanisms underlying PD-L1 deregulation is essential for enhancing the efficacy of PD-L1/PD-1 blockade therapies. As our comprehension of the regulatory mechanisms governing the PD-L1/PD-1 pathway continues to evolve, ongoing exploration of new immunotherapy targets remains critical. This article provides a comprehensive review of recent research concerning the regulation of PD-L1 expression. It encompasses aspects such as its structural characteristics, genomic alterations and rearrangements, epigenetic modifications, inflammatory signaling pathways, oncogenic signaling pathways, microRNA regulation, and post-translational modifications. Additionally, this article illustrates notable advancements and limitations regarding the application of PD-L1 as an immunotherapeutic target in current clinical settings.http://www.sciencedirect.com/science/article/pii/S2589004225008764ImmunologyCancer |
| spellingShingle | Yifei Zhang Keyu Yin Runsheng Ma Yuxiao Sun Longlong Wang Detao Yin Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications iScience Immunology Cancer |
| title | Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications |
| title_full | Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications |
| title_fullStr | Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications |
| title_full_unstemmed | Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications |
| title_short | Complex regulatory network of programmed death-ligand 1 in cancer: Cancer immunomodulation from molecular mechanisms to clinical applications |
| title_sort | complex regulatory network of programmed death ligand 1 in cancer cancer immunomodulation from molecular mechanisms to clinical applications |
| topic | Immunology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225008764 |
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