PXD039893 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Epigenetic therapy activates TE-chimeric transcripts to provide additional source of antigens in glioblastoma stem cells |
Description | Cancer-specific coding mutations can create neoantigens that can be presented on the cell surface of tumors to trigger immunogenic clearance1–4. However, current cancer vaccine approaches have not been universally effective5; this is especially true in tumors with a low mutational burden which, in turn, carry a low conventional neoantigen load6. Transposable elements (TEs) make up approximately 50% of the human genome and have been discovered to provide cryptic promoters, which can be reactivated with epigenetic manipulations to generate TE-gene chimeric transcripts that can be translated into noncanonical peptides7. Here, we focus on glioblastoma, an aggressive brain cancer with low mutation burden, to explore whether epigenetic therapy can induce TE-chimeric antigens (TEAs) to appreciably increase the antigen repertoire that can be targeted with immunotherapy. We perform comprehensive epigenetic and transcriptomic profiling of three patient-derived glioblastoma stem cell lines (GSCs) and, more importantly, astrocyte and fibroblast primary cell lines that are either proliferating or quiescent, treated with epigenetic therapy drugs to identify treatment-induced TEA (TI-TEA) candidates that are preferentially expressed in cancer cells. Although we verify TI-TEAs are indeed presented on HLA molecules in GSCs thus are promising cancer vaccine candidates, many TEs were also transcriptionally activated in proliferating primary cell lines after epigenetic therapy. This work presents a cautionary but optimistic tale for future efforts in harnessing TI-TEAs for targeted immunotherapy approaches. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:43:50.359.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Ju Heon Maeng |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-02-06 05:56:54 | ID requested | |
1 | 2024-06-05 08:12:26 | announced | |
⏵ 2 | 2024-10-22 06:43:50 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: transposable element,Glioblastoma, immunotherapy, epigenetic treatment |
Contact List
Ting Wang |
contact affiliation | Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA |
contact email | twang@wustl.edu |
lab head | |
Ju Heon Maeng |
contact affiliation | Washington University in St. Louis |
contact email | j.maeng@wustl.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039893
- Label: PRIDE project
- Name: Epigenetic therapy activates TE-chimeric transcripts to provide additional source of antigens in glioblastoma stem cells