Melanoma dedifferentiation induced by IFN-γ epigenetic remodeling in response to anti-PD-1 therapy.

Details

Serval ID
serval:BIB_63ED9038D5A4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Melanoma dedifferentiation induced by IFN-γ epigenetic remodeling in response to anti-PD-1 therapy.
Journal
The Journal of clinical investigation
Author(s)
Kim Y.J., Sheu K.M., Tsoi J., Abril-Rodriguez G., Medina E., Grasso C.S., Torrejon D.Y., Champhekar A.S., Litchfield K., Swanton C., Speiser D.E., Scumpia P.O., Hoffmann A., Graeber T.G., Puig-Saus C., Ribas A.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
15/06/2021
Peer-reviewed
Oui
Volume
131
Number
12
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Melanoma dedifferentiation has been reported to be a state of cellular resistance to targeted therapies and immunotherapies as cancer cells revert to a more primitive cellular phenotype. Here, we show that, counterintuitively, the biopsies of patient tumors that responded to anti-programmed cell death 1 (anti-PD-1) therapy had decreased expression of melanocytic markers and increased neural crest markers, suggesting treatment-induced dedifferentiation. When modeling the effects in vitro, we documented that melanoma cell lines that were originally differentiated underwent a process of neural crest dedifferentiation when continuously exposed to IFN-γ, through global chromatin landscape changes that led to enrichment in specific hyperaccessible chromatin regions. The IFN-γ-induced dedifferentiation signature corresponded with improved outcomes in patients with melanoma, challenging the notion that neural crest dedifferentiation is entirely an adverse phenotype.
Keywords
Cancer immunotherapy, Cytokines, Oncology
Pubmed
Open Access
Yes
Create date
19/05/2021 13:58
Last modification date
27/06/2021 6:37
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