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Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors

Author

Listed:
  • Xiaoping Su

    (The University of Texas MD Anderson Cancer Center)

  • Xiaofan Lu

    (Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA
    China Pharmaceutical University)

  • Sehrish Khan Bazai

    (Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA)

  • Linda Dainese

    (Sorbonne Université
    Sorbonne Université
    Sorbonne Université)

  • Arnauld Verschuur

    (Hôpital d’Enfants de La Timone)

  • Benoit Dumont

    (Centre Léon Bérard, Institut d’Hématologie et d’Oncologie Pédiatrique (IHOPe))

  • Roger Mouawad

    (Assistance-Publique Hôpitaux de Paris)

  • Li Xu

    (China Pharmaceutical University)

  • Wenxuan Cheng

    (China Pharmaceutical University)

  • Fangrong Yan

    (China Pharmaceutical University)

  • Sabine Irtan

    (Sorbonne Université)

  • Véronique Lindner

    (CHRU Strasbourg)

  • Catherine Paillard

    (Strasbourg Université)

  • Yves Bouc

    (Sorbonne Université)

  • Aurore Coulomb

    (Sorbonne Université
    Sorbonne Université
    Sorbonne Université)

  • Gabriel G. Malouf

    (Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA
    Strasbourg University)

Abstract

Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell models. We identify histone deacetylase and/or WEE1 inhibitors as potential therapeutic vulnerabilities in these tumors, which might also restore tumor immunogenicity and potentially enhance the effects of immunotherapy. These insights offer a foundation for predicting outcomes and personalizing treatment strategies for aggressive pediatric Wilms tumors, tailored to individual immunological landscapes.

Suggested Citation

  • Xiaoping Su & Xiaofan Lu & Sehrish Khan Bazai & Linda Dainese & Arnauld Verschuur & Benoit Dumont & Roger Mouawad & Li Xu & Wenxuan Cheng & Fangrong Yan & Sabine Irtan & Véronique Lindner & Catherine , 2023. "Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43290-3
    DOI: 10.1038/s41467-023-43290-3
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    1. David A. Barbie & Pablo Tamayo & Jesse S. Boehm & So Young Kim & Susan E. Moody & Ian F. Dunn & Anna C. Schinzel & Peter Sandy & Etienne Meylan & Claudia Scholl & Stefan Fröhling & Edmond M. Chan & Ma, 2009. "Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1," Nature, Nature, vol. 462(7269), pages 108-112, November.
    2. Kosuke Yoshihara & Maria Shahmoradgoli & Emmanuel Martínez & Rahulsimham Vegesna & Hoon Kim & Wandaliz Torres-Garcia & Victor Treviño & Hui Shen & Peter W. Laird & Douglas A. Levine & Scott L. Carter , 2013. "Inferring tumour purity and stromal and immune cell admixture from expression data," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    3. Yujin Hoshida & Jean-Philippe Brunet & Pablo Tamayo & Todd R Golub & Jill P Mesirov, 2007. "Subclass Mapping: Identifying Common Subtypes in Independent Disease Data Sets," PLOS ONE, Public Library of Science, vol. 2(11), pages 1-8, November.
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