biostudies-literatureWirbel CLigue Nationale contre le CancerInstitut National contre le CancerSociété Française de Dermatologie et de Pathologie Sexuellement TransmissibleLyon Integrated Research Institute in CancerAssociation pour la Recherche contre le CancerAgence Régionale de Santé Auvergne Rhône Alpes141https://www.ebi.ac.uk/biostudies/studies/S-EPMC11890833biostudies-literatureUnknown74(4)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, immunotherapy : CIIZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma.PMC11890833INCA-DGOS PRTK_2017-022INCa-DGOS-INSERM-ITMO cancer_18003Balme BCaramel JDalle SEberhardt AGrimont MHarou OLopez JDurand STondeur GPlaschka MBoivin FBenboubker VWirbel CBarbollat-Boutrand LfalseZEB1 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.2025-01-01T00:00:00Z2025 Mar2026-06-01T20:12:55.065Z2025-04-07T07:50:36.863ZS-EPMC118908334005617710.1007/s00262-025-03978-5