ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma

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.

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Publication Details

Journal
Cancer Immunology Immunotherapy
Published
2025-03-08
DOI
https://doi.org/10.1007/s00262-025-03978-5
Citations
4
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
4.18

Funders

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article

ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma

Laetitia Barbollat‐Boutrand, Jonathan Lopez, Maxime Grimont, Valentin Benboubker et al.
4 citations
Cancer Immunology Immunotherapy
Cancer Immunotherapy and Biomarkers
4.18
article

ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma

Laetitia Barbollat‐Boutrand, Jonathan Lopez, Maxime Grimont, Valentin Benboubker, Chloé Wirbel, Maud Plaschka, Stéphane Dalle, Anaïs Eberhardt, Julie Caramel, Olivier Harou, G Tondeur, Simon Durand, Félix Boivin, B. Balme
article en
4 citations

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.

Cancer Immunology ImmunotherapyVol. 74(4)
Université Claude Bernard Lyon 1 (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Hospices Civils de Lyon (FR), Centre Léon Bérard (FR), Centre de Recherche en Cancérologie de Lyon (FR)
Ligue Contre le Cancer, Société Française de Dermatologie et de Pathologie Sexuellement Transmissible
Good health and well-being
Openalex Percentile: Top 6%
Cancer Immunotherapy and Biomarkers
4.18
DOIOpen Access PDFOpenAlex
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