Epigenetic state determines the in vivo efficacy of STING agonist therapy

Rana Falahat, Anders Berglund, Patricio Perez-Villarroel, Ryan M. Putney, Imene Hamaidi, Sungjune Kim, Shari Pilon-Thomas, Glen N. Barber and James J. Mulé ()
Additional contact information
Rana Falahat: Moffitt Cancer Center
Anders Berglund: Moffitt Cancer Center
Patricio Perez-Villarroel: Moffitt Cancer Center
Ryan M. Putney: Moffitt Cancer Center
Imene Hamaidi: Moffitt Cancer Center
Sungjune Kim: Moffitt Cancer Center
Shari Pilon-Thomas: Moffitt Cancer Center
Glen N. Barber: University of Miami Miller School of Medicine
James J. Mulé: Moffitt Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract While STING-activating agents have shown limited efficacy in early-phase clinical trials, multiple lines of evidence suggest the importance of tumor cell-intrinsic STING function in mediating antitumor immune responses. Although STING signaling is impaired in human melanoma, its restoration through epigenetic reprogramming can augment its antigenicity and T cell recognition. In this study, we show that reversal of methylation silencing of STING in murine melanoma cell lines using a clinically available DNA methylation inhibitor can improve agonist-induced STING activation and type-I IFN induction, which, in tumor-bearing mice, can induce tumor regression through a CD8+ T cell-dependent immune response. These findings not only provide mechanistic insight into how STING signaling dysfunction in tumor cells can contribute to impaired responses to STING agonist therapy, but also suggest that pharmacological restoration of STING signaling through epigenetic reprogramming might improve the therapeutic efficacy of STING agonists.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37217-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37217-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37217-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().