The screening of compounds regulating PD‐L1 transcriptional activity in a cell functional high‐throughput manner
Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune checkpoint, overexpressed PD‐1 on tumor cells could inhibit T‐cell activation after being bonded to PD‐1. Due to this inhibitory effect, T‐cell...
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Published in | Cancer medicine (Malden, MA) Vol. 12; no. 8; pp. 9815 - 9825 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
John Wiley & Sons, Inc
01.04.2023
John Wiley and Sons Inc Wiley |
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Abstract | Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune checkpoint, overexpressed PD‐1 on tumor cells could inhibit T‐cell activation after being bonded to PD‐1. Due to this inhibitory effect, T‐cell proliferation and cytokine secretion are suppressed, leading to immune escape of tumor cells. Here, we established a high‐throughput method based on cell function screening technology to screen drugs regulating PD‐L1 expression in tumor cells at the transcriptional level. After two screening rounds, 12 compounds that enhanced PD‐L1 transcription while seven weakened were sorted out among 1018 FDA‐approved drugs. Finally, a tumor cell line was used to verify the upregulation of endogenous PD‐L1 expression for a drug named “vorinostat,” a histone deacetylation inhibitor, after the two rounds of optional selection. Therefore, our research provides another perspective for using “vorinostat” in treating tumors and offers a convenient method to detect the transcriptional expression of other intracellular proteins besides PD‐L1.
The screening process of small molecular chemical drugs regulating transcriptional PD‐L1 via cell‐based high‐throughput screening system. |
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AbstractList | Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune checkpoint, overexpressed PD-1 on tumor cells could inhibit T-cell activation after being bonded to PD-1. Due to this inhibitory effect, T-cell proliferation and cytokine secretion are suppressed, leading to immune escape of tumor cells. Here, we established a high-throughput method based on cell function screening technology to screen drugs regulating PD-L1 expression in tumor cells at the transcriptional level. After two screening rounds, 12 compounds that enhanced PD-L1 transcription while seven weakened were sorted out among 1018 FDA-approved drugs. Finally, a tumor cell line was used to verify the upregulation of endogenous PD-L1 expression for a drug named “vorinostat,” a histone deacetylation inhibitor, after the two rounds of optional selection. Therefore, our research provides another perspective for using “vorinostat” in treating tumors and offers a convenient method to detect the transcriptional expression of other intracellular proteins besides PD-L1. Abstract Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune checkpoint, overexpressed PD‐1 on tumor cells could inhibit T‐cell activation after being bonded to PD‐1. Due to this inhibitory effect, T‐cell proliferation and cytokine secretion are suppressed, leading to immune escape of tumor cells. Here, we established a high‐throughput method based on cell function screening technology to screen drugs regulating PD‐L1 expression in tumor cells at the transcriptional level. After two screening rounds, 12 compounds that enhanced PD‐L1 transcription while seven weakened were sorted out among 1018 FDA‐approved drugs. Finally, a tumor cell line was used to verify the upregulation of endogenous PD‐L1 expression for a drug named “vorinostat,” a histone deacetylation inhibitor, after the two rounds of optional selection. Therefore, our research provides another perspective for using “vorinostat” in treating tumors and offers a convenient method to detect the transcriptional expression of other intracellular proteins besides PD‐L1. Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune checkpoint, overexpressed PD‐1 on tumor cells could inhibit T‐cell activation after being bonded to PD‐1. Due to this inhibitory effect, T‐cell proliferation and cytokine secretion are suppressed, leading to immune escape of tumor cells. Here, we established a high‐throughput method based on cell function screening technology to screen drugs regulating PD‐L1 expression in tumor cells at the transcriptional level. After two screening rounds, 12 compounds that enhanced PD‐L1 transcription while seven weakened were sorted out among 1018 FDA‐approved drugs. Finally, a tumor cell line was used to verify the upregulation of endogenous PD‐L1 expression for a drug named “vorinostat,” a histone deacetylation inhibitor, after the two rounds of optional selection. Therefore, our research provides another perspective for using “vorinostat” in treating tumors and offers a convenient method to detect the transcriptional expression of other intracellular proteins besides PD‐L1. The screening process of small molecular chemical drugs regulating transcriptional PD‐L1 via cell‐based high‐throughput screening system. Abstract Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune checkpoint, overexpressed PD‐1 on tumor cells could inhibit T‐cell activation after being bonded to PD‐1. Due to this inhibitory effect, T‐cell proliferation and cytokine secretion are suppressed, leading to immune escape of tumor cells. Here, we established a high‐throughput method based on cell function screening technology to screen drugs regulating PD‐L1 expression in tumor cells at the transcriptional level. After two screening rounds, 12 compounds that enhanced PD‐L1 transcription while seven weakened were sorted out among 1018 FDA‐approved drugs. Finally, a tumor cell line was used to verify the upregulation of endogenous PD‐L1 expression for a drug named “vorinostat,” a histone deacetylation inhibitor, after the two rounds of optional selection. Therefore, our research provides another perspective for using “vorinostat” in treating tumors and offers a convenient method to detect the transcriptional expression of other intracellular proteins besides PD‐L1. |
Author | Li, Hexin Zhang, Lili Xu, Siyuan Zhang, Lanxin Sun, Gaoyuan Zhang, Wei Ai, Bin Liu, Jingchao Tang, Xiaokun |
AuthorAffiliation | 2 Department of Urology, Beijing Hospital, National Center of Gerontology Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China 3 Department of Pathology, Beijing Hospital, National Center of Gerontology, National Health Commission Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China 4 Department of Medical Oncology, Beijing Hospital, National Center of Gerontology, National Health Commission Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China 1 Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China |
AuthorAffiliation_xml | – name: 3 Department of Pathology, Beijing Hospital, National Center of Gerontology, National Health Commission Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China – name: 2 Department of Urology, Beijing Hospital, National Center of Gerontology Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China – name: 4 Department of Medical Oncology, Beijing Hospital, National Center of Gerontology, National Health Commission Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China – name: 1 Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing China |
Author_xml | – sequence: 1 givenname: Lanxin orcidid: 0000-0002-6088-1538 surname: Zhang fullname: Zhang, Lanxin organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 2 givenname: Hexin surname: Li fullname: Li, Hexin organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 3 givenname: Jingchao surname: Liu fullname: Liu, Jingchao organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 4 givenname: Gaoyuan surname: Sun fullname: Sun, Gaoyuan organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 5 givenname: Xiaokun surname: Tang fullname: Tang, Xiaokun organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 6 givenname: Siyuan surname: Xu fullname: Xu, Siyuan organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 7 givenname: Lili surname: Zhang fullname: Zhang, Lili organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 8 givenname: Wei surname: Zhang fullname: Zhang, Wei email: zhangwei3392@bjhmoh.cn organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences – sequence: 9 givenname: Bin surname: Ai fullname: Ai, Bin email: docaibin@163.com organization: Institute of Geriatric Medicine, Chinese Academy of Medical Sciences |
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Cites_doi | 10.1002/cam4.3410 10.1016/j.jss.2019.02.038 10.1038/nrd.2018.168 10.5599/admet.4.1.276 10.1186/s12943-019-0974-6 10.1016/j.ijcha.2019.100420 10.1016/j.ejmech.2021.113284 10.1016/j.lfs.2020.118239 10.1016/B978-0-12-817661-0.00008-1 10.1111/j.1600-065X.2010.00923.x 10.3389/fimmu.2021.690869 10.1186/s12935-020-01545-9 10.1097/CAD.0000000000001055 10.4103/ijo.IJO_2056_18 10.1186/s12943-018-0928-4 10.1016/j.drudis.2019.06.014 10.1111/php.13300 10.1016/j.intimp.2021.107403 10.3390/ijms20194794 10.2147/OTT.S221340 10.1002/jcp.28358 10.1016/j.ejmech.2021.113473 10.1111/jcmm.14027 10.1182/blood.2019001043 10.3389/fimmu.2016.00684 10.1016/j.intimp.2018.06.001 10.3390/pathogens10121540 10.1111/j.1749-6632.2010.05919.x |
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Copyright | 2023 The Authors. published by John Wiley & Sons Ltd. 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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Snippet | Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune... Abstract Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential... Abstract Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential... |
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SubjectTerms | B7-H1 Antigen - metabolism cancer Cell activation Cell Line, Tumor Cell membranes Cell proliferation Cells Cytokines Deacetylation Drug screening Drugs FDA approval Growth factors high‐throughput screen Histones Humans Immune checkpoint Immune system Immunosuppressive agents Kinases Laboratories Lymphocytes T Mutation PD-1 protein PD-L1 protein PD‐L1 Polymerase chain reaction Programmed Cell Death 1 Receptor - metabolism Proteins Transcription Tumor cell lines Tumor cells Tumor necrosis factor-TNF Tumors vorinostat |
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Title | The screening of compounds regulating PD‐L1 transcriptional activity in a cell functional high‐throughput manner |
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