PXD039893

PXD039893 is an original dataset announced via ProteomeXchange.

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	2024-06-05
AnnouncementXML	Submission_2024-06-05_08:12:25.794.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

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-06 05:56:54	ID requested
⏵ 1	2024-06-05 08:12:26	announced

Dataset with its publication pending

submitter keyword: transposable element,Glioblastoma, immunotherapy, epigenetic treatment

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

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/2024/06/PXD039893

PRIDE project URI

• PRIDE
  1. PXD039893
     1. Label: PRIDE project
     2. Name: Epigenetic therapy activates TE-chimeric transcripts to provide additional source of antigens in glioblastoma stem cells