Nonsense-mediated mRNA decay inhibition reshapes the cancer immunopeptidome - PubMed
6 hours ago
- #NMD inhibition
- #cancer immunopeptidome
- #neoantigen therapy
- Inhibition of nonsense-mediated mRNA decay (NMD) through SMG1 targeting improves checkpoint inhibitor response in over 1,000 patients.
- NMD inhibition stabilizes non-mutational transcripts with premature termination codons, reshaping the MHC class I immunopeptidome and increasing neoantigen levels.
- The strategy enhances T cell-mediated tumor killing in vitro, activates tissue-resident T cells ex vivo, and boosts immunotherapy efficacy in vivo.
- NMD inhibition unlocks canonical and non-canonical neoantigens, potentially broadening tumor immunogenicity across various cancers.