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

• DOI: 10.1007/s00262-025-03978-5
• Publication Date: 2025-03-08T13:38:22Z
• Authors: Chloé Wirbel; Simon Durand; Félix Boivin; Maud Plaschka; Valentin Benboubker; Maxime Grimont; Laetitia Barbolla...; Garance Tondeur; Brigitte Balme; Olivier Harou; Anaïs Eberhardt; Stéphane Dalle; Jonathan Lopez; Julie Caramel
• Keywords: Transcription

Tumor cells can evade antitumor immune response by expressing the PD-L1 ligand, leading to inhibition of PD-1-expressing T lymphocytes. The mechanisms that regulate expression in cancer are imperfectly characterized. transcription factor ZEB1, a major regulator phenotype switching melanoma cells, was shown promote escape repressing cell infiltration. Using inducible models and ZEB1 gain/loss-of-function melanoma, we show binds CD274 (PD-L1) promoter, directly enhancing mRNA its at membrane. Furthermore, using single-cell spatial analyses on human primary samples, demonstrate correlation tumor cells. Overall, these data identify ZEB1-mediated regulation as mechanism could contribute melanoma.