ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma
Abstract Tumor cells can evade antitumor immune response by expressing the PD-L1 ligand, leading to the inhibition of PD-1-expressing T lymphocytes. The mechanisms that regulate PD-L1 expression in cancer cells are imperfectly characterized. The transcription factor ZEB1, a major regulator of phenot...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2025-03-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03978-5 |
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| author | Chloé Wirbel Simon Durand Félix Boivin Maud Plaschka Valentin Benboubker Maxime Grimont Laetitia Barbollat-Boutrand Garance Tondeur Brigitte Balme Olivier Harou Anaïs Eberhardt Stéphane Dalle Jonathan Lopez Julie Caramel |
| author_facet | Chloé Wirbel Simon Durand Félix Boivin Maud Plaschka Valentin Benboubker Maxime Grimont Laetitia Barbollat-Boutrand Garance Tondeur Brigitte Balme Olivier Harou Anaïs Eberhardt Stéphane Dalle Jonathan Lopez Julie Caramel |
| author_sort | Chloé Wirbel |
| collection | DOAJ |
| description | Abstract Tumor cells can evade antitumor immune response by expressing the PD-L1 ligand, leading to the inhibition of PD-1-expressing T lymphocytes. The mechanisms that regulate PD-L1 expression in cancer cells are imperfectly characterized. The transcription factor ZEB1, a major regulator of phenotype switching in melanoma cells, was shown to promote immune escape in melanoma by repressing T cell infiltration. Using inducible models of phenotype switching and ZEB1 gain/loss-of-function melanoma, we show that ZEB1 binds to the CD274 (PD-L1) promoter, directly enhancing PD-L1 mRNA transcription and its expression at the cell membrane. Furthermore, using single-cell spatial analyses on human primary melanoma samples, we demonstrate the correlation of ZEB1 and PD-L1 expression in tumor cells. Overall, these data identify ZEB1-mediated regulation of PD-L1 tumor expression as a mechanism that could contribute to immune escape in melanoma. |
| format | Article |
| id | doaj-art-842cf89e280c42a78d076f1f7cb89a3a |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-842cf89e280c42a78d076f1f7cb89a3a2025-08-20T02:49:35ZengSpringerCancer Immunology, Immunotherapy1432-08512025-03-017441910.1007/s00262-025-03978-5ZEB1 transcription factor induces tumor cell PD-L1 expression in melanomaChloé Wirbel0Simon Durand1Félix Boivin2Maud Plaschka3Valentin Benboubker4Maxime Grimont5Laetitia Barbollat-Boutrand6Garance Tondeur7Brigitte Balme8Olivier Harou9Anaïs Eberhardt10Stéphane Dalle11Jonathan Lopez12Julie Caramel13Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamDermatology Unit, Hospices Civils de Lyon, CH Lyon SudDermatology Unit, Hospices Civils de Lyon, CH Lyon SudDermatology Unit, Hospices Civils de Lyon, CH Lyon SudCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamCancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, “Cancer Cell Plasticity in Melanoma” TeamAbstract Tumor cells can evade antitumor immune response by expressing the PD-L1 ligand, leading to the inhibition of PD-1-expressing T lymphocytes. The mechanisms that regulate PD-L1 expression in cancer cells are imperfectly characterized. The transcription factor ZEB1, a major regulator of phenotype switching in melanoma cells, was shown to promote immune escape in melanoma by repressing T cell infiltration. Using inducible models of phenotype switching and ZEB1 gain/loss-of-function melanoma, we show that ZEB1 binds to the CD274 (PD-L1) promoter, directly enhancing PD-L1 mRNA transcription and its expression at the cell membrane. Furthermore, using single-cell spatial analyses on human primary melanoma samples, we demonstrate the correlation of ZEB1 and PD-L1 expression in tumor cells. Overall, these data identify ZEB1-mediated regulation of PD-L1 tumor expression as a mechanism that could contribute to immune escape in melanoma.https://doi.org/10.1007/s00262-025-03978-5MelanomaZEB1PD-L1Phenotype switchingPseudo-EMT |
| spellingShingle | Chloé Wirbel Simon Durand Félix Boivin Maud Plaschka Valentin Benboubker Maxime Grimont Laetitia Barbollat-Boutrand Garance Tondeur Brigitte Balme Olivier Harou Anaïs Eberhardt Stéphane Dalle Jonathan Lopez Julie Caramel ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma Cancer Immunology, Immunotherapy Melanoma ZEB1 PD-L1 Phenotype switching Pseudo-EMT |
| title | ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma |
| title_full | ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma |
| title_fullStr | ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma |
| title_full_unstemmed | ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma |
| title_short | ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma |
| title_sort | zeb1 transcription factor induces tumor cell pd l1 expression in melanoma |
| topic | Melanoma ZEB1 PD-L1 Phenotype switching Pseudo-EMT |
| url | https://doi.org/10.1007/s00262-025-03978-5 |
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