Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
02 Mar 2023
02 Mar 2023
Historique:
received:
25
08
2022
accepted:
10
02
2023
entrez:
2
3
2023
pubmed:
3
3
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse melanoma models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently of tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation in expression, leading to tumor heterogeneity and subclonal resistance.
Identifiants
pubmed: 36864091
doi: 10.1038/s41698-023-00362-3
pii: 10.1038/s41698-023-00362-3
pmc: PMC9981575
doi:
Types de publication
Journal Article
Langues
eng
Pagination
25Subventions
Organisme : NCI NIH HHS
ID : R01 CA129933
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Informations de copyright
© 2023. The Author(s).
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