PXD035750-2

PXD035750 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 neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies synergize with immunotherapies, mediated bythe de-repression of endogenous retroviral element (ERV)-encoded promoters, and the initiation of transcription. Here, we use deep RNA sequencing from cancer cell lines treated with DNA methyltransferase inhibitors (DNMTi) and/or Histone deacetylase transferase inhibitors (HDACi), to assemble a de novo transcriptome and identified 3,023 ERV-derived, treatment-induced novel polyadenylated transcripts (TINPATs), encoding for 61,426 open reading frames. Using Immunopeptidomics, we further demonstrate the human leukocyte antigen (HLA) presentation of treatment-induced neoepitopes (t-neoepitopes) derived from TINPATs. We illustrate the potential of the identified t-neoepitopes to elicit a T-cell response and cancer cell killing. The presence of t-neoepitopes was further verified in AML patient samples 48/96 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_06:00:47.390.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jens Bauer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-02 10:33:08	ID requested
1	2023-08-18 06:10:51	announced
⏵ 2	2024-10-22 06:00:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

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

Professor Juliane Walz
contact affiliation	Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany (lab head)
contact email	juliane.walz@med.uni-tuebingen.de
lab head
Jens Bauer
contact affiliation	Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
contact email	j.bauer@uni-tuebingen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035750
     1. Label: PRIDE project
     2. Name: DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts