PXD035748-2

PXD035748 is an original dataset announced via ProteomeXchange.

Title	DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts
Description	Immunotherapies targeting cancer-specific immunogenic neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies could synergize with immunotherapies, mediating the de-repression of endogenous retroviral element (ERV)-encoded promoters, and the initiation of transcription. Here we use RNA sequencing from cancer cells treated with DNMT and/or HDAC inhibitors, to assemble a de novo transcriptome and identified 3,023 ERV-derived, treatment-induced novel polA+ transcripts (TINPATs), encoding for 61,426 novel open reading frames. We further demonstrate, using human leukocyte antigen immunopeptidomics, the existence of treatment-induced neoepitopes (t-neoepitopes) derived from TINPATs. We demonstrated the potential of the identified t-neoepitopes to elicit an immunogenic T-cell response and cancer cell killing. The presence of t-neoepitopes was further verified in AML patient samples 48 h and /96 h after in vivo treatment with the DNMT inhibitor Decitabine. Our findings highlight a novel mechanism of ERV-derived neoantigens in epigenetic and immune therapies.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:03:04.795.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dimitris Papageorgiou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-02 10:31:34	ID requested
1	2023-09-13 04:27:42	announced
⏵ 2	2024-10-22 06:03:05	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Decitabine,DNMT, HLA, LTR, Cancer, ERV, MHC, Neoantigen, HDAC, SB939, Immunopeptidomics, Immunotherapy

Jeroen Krijgsveld
contact affiliation	Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany Heidelberg University, Medical Faculty, Heidelberg, Germany
contact email	j.krijgsveld@dkfz-heidelberg.de
lab head
Dimitris Papageorgiou
contact affiliation	Post-Doctoral Scientist
contact email	d.papageorgiou@dkfz.de
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/2023/09/PXD035748

PRIDE project URI

• PRIDE
  1. PXD035748
     1. Label: PRIDE project
     2. Name: DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts