Epigenetic state determines the in vivo efficacy of STING agonist therapy.

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

SUBMITTER: Falahat R 

PROVIDER: S-EPMC10033671 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature