Goyal, Ashish; Bauer, Jens; Hey, Joschka; Papageorgiou, Dimitris N; Stepanova, Ekaterina; Daskalakis, Michael; Scheid, Jonas; Dubbelaar, Marissa; Klimovich, Boris; Schwarz, Dominic; Märklin, Melanie; Roerden, Malte; Lin, Yu-Yu; Ma, Tobias; Mücke, Oliver; Rammensee, Hans-Georg; Lübbert, Michael; Loayza-Puch, Fabricio; Krijgsveld, Jeroen; Walz, Juliane S; ... (2023). DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts. Nature communications, 14(1), p. 6731. Nature Publishing Group 10.1038/s41467-023-42417-w
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory |
UniBE Contributor: |
Daskalakis, Michael |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
24 Oct 2023 09:31 |
Last Modified: |
29 Oct 2023 02:26 |
Publisher DOI: |
10.1038/s41467-023-42417-w |
PubMed ID: |
37872136 |
BORIS DOI: |
10.48350/187401 |
URI: |
https://boris.unibe.ch/id/eprint/187401 |
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