PXD073256-1

PXD073256 is an original dataset announced via ProteomeXchange.

Title	Pharmacological inhibition of nonsense-mediated mRNA decay enhances anti-tumor immunity
Description	Frameshift insertion/deletions can produce highly immunogenic neoantigens; however, frameshift-derived transcripts are often degraded by the nonsense-mediated mRNA decay (NMD) pathway. Leveraging multiomics and checkpoint in-hibitor (CPI) response data from over 1,000 patients, we demonstrate that reduced expression or genetic loss of the NMD mediator SMG1 correlates with improved CPI responses. SMG1 inhibition ex vivo and in vivo activates and expands tumour-reactive lymphocytes and potentiates CPI responses. Mechanistically, SMG1 inhibi-tion stabilises frameshift-derived transcripts and increases the abundance and sur-face presentation of immunogenic neoantigens, shifting the neoepitope count from a low- to a high-tumour mutational burden (TMB)-like state without causing DNA damage. Co-culture of lymphocytes with tumour cells upon SMG1i induces antigen-dependent T cell activation and tumour cell killing. Our findings highlight SMG1 in-hibition as a promising immuno-oncology strategy to harness an untapped source of immunogenic neoantigens to enhance tumour immunogenicity and improve CPI efficacy, with broad applicability irrespective of TMB status.
HostingRepository	PRIDE
AnnounceDate	2026-04-07
AnnouncementXML	Submission_2026-04-07_13:16:38.025.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chen Weller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-19 17:44:19	ID requested
⏵ 1	2026-04-07 13:16:38	announced

10.1016/J.IMMUNI.2026.02.005.;

submitter keyword: NMD, Immunopeptidomics, Class_I

Yardena Samuels
contact affiliation	Weizmann Institute of Science
contact email	yardena.samuels@weizmann.ac.il
lab head
Chen Weller
contact affiliation	Yardena Samuels lab, Weizmann Institute of Science
contact email	chen.weller@weizmann.ac.il
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073256

PRIDE project URI

• PRIDE
  1. PXD073256
     1. Label: PRIDE project
     2. Name: Pharmacological inhibition of nonsense-mediated mRNA decay enhances anti-tumor immunity