articleCellJan 1, 2024HYBRID OA

A TCF4-dependent gene regulatory network confers resistance to immunotherapy in melanoma

JPJoanna PoźniakDPDennis PedriELEwout LandeloosYVYannick Van HerckAAAsier Antoranz

VIB-KU Leuven Center for Cancer Biology · KU Leuven · +12 more institutions

PubMed
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Abstract

To better understand intrinsic resistance to immune checkpoint blockade (ICB), we established a comprehensive view of the cellular architecture of the treatment-naive melanoma ecosystem and studied its evolution under ICB. Using single-cell, spatial multi-omics, we showed that the tumor microenvironment promotes the emergence of a complex melanoma transcriptomic landscape. Melanoma cells harboring a mesenchymal-like (MES) state, a population known to confer resistance to targeted therapy, were significantly enriched in early on-treatment biopsies from non-responders to ICB. TCF4 serves as the hub of this landscape by being a master regulator of the MES signature and a suppressor of the melanocytic and antigen…

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Authors

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Topics & keywords

Topics
Keywords
  • Biology
  • Melanoma
  • Immunotherapy
  • Transcriptome
  • Cancer research
  • Immune checkpoint
  • TCF4
  • Gene regulatory network
UN Sustainable Development Goals
  • Life in Land
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