PXD053256

PXD053256 is an original dataset announced via ProteomeXchange.

Title	Translation dysregulation in cancer as a source for targetable antigens
Description	Aberrant peptides presented by major histocompatibility complex (MHC) molecules are targets for tumor eradication, as these peptides can be recognized as foreign by T cells. Protein synthesis in malignant cells is dysregulated, resulting in the production of non-canonical aberrant peptides. We hypothesized that inducing translation aberrations in cancers might reveal neopeptides that can be exploited for T cell-based therapies. To explore this hypothesis, we disrupted translation fidelity by silencing TYW2, a tRNA-yW synthesizing Protein 2 that supports reading-frame maintenance. Using ribosome profiling coupled with immunopeptidomics, we uncover a large set of out-of-frame peptides in TYW2 KO cells and demonstrate that these aberrant peptides are highly immunogenic. Furthermore, we show that Tyw2 loss leads to increased immunogenicity of melanoma tumors in vivo, mediated through cytotoxic T cell activity. Importantly, treatment of Tyw2 KO tumor-bearing mice with anti-PD1 checkpoint blockade therapy further reduces tumor growth, and its reduced expression is associated with increased response to checkpoint blockade therapy in patients. Together, our data shows that defects in translation fidelity indeed contribute to tumor immunogenicity and suggests that they can be harnessed for cancer immunotherapy modalities.
HostingRepository	PRIDE
AnnounceDate	2025-03-25
AnnouncementXML	Submission_2025-03-25_11:45:39.316.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chen Weller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-20 08:50:33	ID requested
⏵ 1	2025-03-25 11:45:39	announced

10.1016/J.CCELL.2025.03.003.;

submitter keyword: Human, MAPP, Cancer, Proteome, Mice, Immunopeptidome

Yardena Samuels
contact affiliation	Molecular cell biology, 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/2025/03/PXD053256

PRIDE project URI

• PRIDE
  1. PXD053256
     1. Label: PRIDE project
     2. Name: Translation dysregulation in cancer as a source for targetable antigens