Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
received:
13
01
2023
accepted:
06
11
2023
medline:
4
12
2023
pubmed:
1
12
2023
entrez:
30
11
2023
Statut:
epublish
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.
Identifiants
pubmed: 38036539
doi: 10.1038/s41467-023-43290-3
pii: 10.1038/s41467-023-43290-3
pmc: PMC10689851
doi:
Substances chimiques
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7884Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA096300
Pays : United States
Informations de copyright
© 2023. The Author(s).
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