PXD059832-1

PXD059832 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Cancer-restricted cryptic antigens are targets for T cell recognition
Description	Ely ZA, Kulstad ZJ, Gunaydin G, Addepalli S, Verzani EK, Casarrubios M, Clauser KR, Wang X, Lippincott IE, Louvet C, Schmitt T, Kapner KS, Agus MP, Hennessey CJ, Cleary JM, Hadrup SR, Klaeger S, Su J, Jaeger AM, Wolpin BM, Raghavan S, Smith EL, Greenberg PD, Aguirre AJ, Abelin JG, Carr SA, Jacks T, Freed-Pastor WA. 2025 Translation of the non-coding genome in cancer can generate cryptic peptides capable of presentation by human leukocyte antigen class I (HLA-I); however, the cancer-specificity and immunogenicity of non-canonical HLA-I-bound peptides (ncHLAp) is not fully understood. Using personalized proteogenomics coupled with high-resolution immunopeptidomics, we found that cryptic peptides are abundant in the pancreatic cancer immunopeptidome. We developed a novel translation-centric pipeline and discovered that ~30% of ncHLAp exhibit bona fide cancer-restricted translation, with a substantial subset shared among patients. Cancer-restricted ncHLAp demonstrated immunogenic potential in a highly sensitive ex vivo T cell priming platform. ncHLAp-reactive, TCR-redirected T cells (TCR-T) exhibit robust tumoricidal activity against patient-derived pancreatic cancer organoids. These findings demonstrate that dysregulated translation in pancreatic cancer can give rise to recurrent cancer-restricted ncHLAp capable of recognition by cytotoxic T cells. We anticipate future therapeutic strategies for pancreatic cancer and other solid tumors will include targeting cryptic antigens.
HostingRepository	MassIVE
AnnounceDate	2025-01-23
AnnouncementXML	Submission_2025-01-23_03:49:51.718.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karl Clauser
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	unknown modification; unknown modification; unknown modification; unknown modification
Instrument	Orbitrap Exploris 480

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-15 12:00:52	ID requested
⏵ 1	2025-01-23 03:49:52	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: immunopeptidome, pancreatic ductal adenocarcinoma, non-canonical ORF, DatasetType:Proteomics

submitter keyword: immunopeptidome, pancreatic ductal adenocarcinoma, non-canonical ORF, DatasetType:Proteomics

Contact List

Steven A. Carr
contact affiliation	Broad Institute of MIT and Harvard
contact email	scarr@broadinstitute.org
lab head
Karl Clauser
contact affiliation	Broad Institute of MIT and Harvard
contact email	clauser@broadinstitute.org
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

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://massive.ucsd.edu/v06/MSV000096853/