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Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer

Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib d...

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Autores principales: Chen, Xi, Du, Qianqian, Guo, Hongjie, He, Qiaojun, Yang, Bo, Ding, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201485/
https://www.ncbi.nlm.nih.gov/pubmed/35721177
http://dx.doi.org/10.3389/fphar.2022.897747
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author Chen, Xi
Du, Qianqian
Guo, Hongjie
He, Qiaojun
Yang, Bo
Ding, Ling
author_facet Chen, Xi
Du, Qianqian
Guo, Hongjie
He, Qiaojun
Yang, Bo
Ding, Ling
author_sort Chen, Xi
collection PubMed
description Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib dramatically suppresses PD-L1 protein expression in a dose-dependent manner. In parallel, cell membrane PD-L1 is also reduced by Bafetinib. We confirm that Bafetinib doesn’t affect the protein half-life of PD-L1 but significantly inhibits the transcription of PD-L1. Among the transcription factors that regulate PD-L1 expression, c-Myc is downregulated by Bafetinib. Bafetinib caused PD-L1 inhibition is abolished when c-Myc is knocked-down. Further, we identified that Bafetinib reduced c-Myc expression because of transcription inhibition. By using the CT26 tumor model, we further confirm that Bafetinib suppressed PD-L1 expression in vivo. In conclusion, our study shows that Bafetinib inhibits the transcription of PD-L1 through transcription factor c-Myc, suggesting that Bafetinib might be a small molecule drug targeting PD-L1.
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spelling pubmed-92014852022-06-17 Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer Chen, Xi Du, Qianqian Guo, Hongjie He, Qiaojun Yang, Bo Ding, Ling Front Pharmacol Pharmacology Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib dramatically suppresses PD-L1 protein expression in a dose-dependent manner. In parallel, cell membrane PD-L1 is also reduced by Bafetinib. We confirm that Bafetinib doesn’t affect the protein half-life of PD-L1 but significantly inhibits the transcription of PD-L1. Among the transcription factors that regulate PD-L1 expression, c-Myc is downregulated by Bafetinib. Bafetinib caused PD-L1 inhibition is abolished when c-Myc is knocked-down. Further, we identified that Bafetinib reduced c-Myc expression because of transcription inhibition. By using the CT26 tumor model, we further confirm that Bafetinib suppressed PD-L1 expression in vivo. In conclusion, our study shows that Bafetinib inhibits the transcription of PD-L1 through transcription factor c-Myc, suggesting that Bafetinib might be a small molecule drug targeting PD-L1. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201485/ /pubmed/35721177 http://dx.doi.org/10.3389/fphar.2022.897747 Text en Copyright © 2022 Chen, Du, Guo, He, Yang and Ding. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chen, Xi
Du, Qianqian
Guo, Hongjie
He, Qiaojun
Yang, Bo
Ding, Ling
Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
title Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
title_full Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
title_fullStr Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
title_full_unstemmed Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
title_short Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
title_sort bafetinib suppresses the transcription of pd-l1 through c-myc in lung cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201485/
https://www.ncbi.nlm.nih.gov/pubmed/35721177
http://dx.doi.org/10.3389/fphar.2022.897747
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