Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors.
Fiche publication
Date publication
novembre 2023
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LINDNER Véronique, Pr MALOUF Gabriel
Tous les auteurs :
Su X, Lu X, Bazai SK, Dainese L, Verschuur A, Dumont B, Mouawad R, Xu L, Cheng W, Yan F, Irtan S, Lindner V, Paillard C, Le Bouc Y, Coulomb A, Malouf GG
Lien Pubmed
Résumé
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.
Mots clés
Child, Humans, Kidney Neoplasms, genetics, Wilms Tumor, genetics, Histone Deacetylases
Référence
Nat Commun. 2023 11 30;14(1):7884