DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

Ashish Goyal, Jens Bauer, Joschka Hey, Dimitris N. Papageorgiou, Ekaterina Stepanova, Michael Daskalakis, Jonas Scheid, Marissa Dubbelaar, Boris Klimovich, Dominic Schwarz, Melanie Märklin, Malte Roerden, Yu-Yu Lin, Tobias Ma, Oliver Mücke, Hans-Georg Rammensee, Michael Lübbert, Fabricio Loayza-Puch, Jeroen Krijgsveld, Juliane S. Walz () and Christoph Plass ()
Additional contact information
Ashish Goyal: German Cancer Research Center (DKFZ)
Jens Bauer: University of Tübingen and University Hospital Tübingen
Joschka Hey: German Cancer Research Center (DKFZ)
Dimitris N. Papageorgiou: German Cancer Research Center (DKFZ)
Ekaterina Stepanova: German Cancer Research Center (DKFZ)
Michael Daskalakis: German Cancer Research Center (DKFZ)
Jonas Scheid: University of Tübingen and University Hospital Tübingen
Marissa Dubbelaar: University of Tübingen and University Hospital Tübingen
Boris Klimovich: University of Tübingen
Dominic Schwarz: German Cancer Research Center (DKFZ)
Melanie Märklin: University of Tübingen
Malte Roerden: University of Tübingen and University Hospital Tübingen
Yu-Yu Lin: German Cancer Research Center (DKFZ)
Tobias Ma: University Medical Center Freiburg, Faculty of Medicine, University of Freiburg
Oliver Mücke: German Cancer Research Center (DKFZ)
Hans-Georg Rammensee: University of Tübingen
Michael Lübbert: University Medical Center Freiburg, Faculty of Medicine, University of Freiburg
Fabricio Loayza-Puch: German Cancer Research Center (DKFZ)
Jeroen Krijgsveld: German Cancer Research Center (DKFZ)
Juliane S. Walz: University of Tübingen and University Hospital Tübingen
Christoph Plass: German Cancer Research Center (DKFZ)

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Immunotherapies targeting cancer-specific neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies synergize with immunotherapies, mediated by the 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 inhibitor (DNMTi) and/or Histone deacetylase inhibitor (HDACi), to assemble a de novo transcriptome and identify several thousand ERV-derived, treatment-induced novel polyadenylated transcripts (TINPATs). Using immunopeptidomics, we demonstrate the human leukocyte antigen (HLA) presentation of 45 spectra-validated treatment-induced neopeptides (t-neopeptides) arising from TINPATs. We illustrate the potential of the identified t-neopeptides to elicit a T-cell response to effectively target cancer cells. We further verify the presence of t-neopeptides in AML patient samples after in vivo treatment with the DNMT inhibitor Decitabine. Our findings highlight the potential of ERV-derived neoantigens in epigenetic and immune therapies.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42417-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42417-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-42417-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().