Journal Article

DKFZ-2023-02154

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts.

Goyal, A. (First author)DKFZ* ; Bauer, J. ; Hey, J. (First author)DKFZ* ; Papageorgiou, D. N.DKFZ* ; Stepanova, E. ; Daskalakis, M.DKFZ* ; Scheid, J. ; Dubbelaar, M. ; Klimovich, B.DKFZ* ; Schwarz, D.DKFZ* ; Märklin, M.DKFZ* ; Roerden, M. ; Lin, Y.-Y.DKFZ* ; Ma, T. ; Mücke, O.DKFZ* ; Rammensee, H.-G.DKFZ* ; Lübbert, M. ; Loayza-Puch, F.DKFZ* ; Krijgsveld, J.DKFZ* ; Walz, J.DKFZ* ; Plass, C. (Last author)DKFZ*

2023
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-023-42417-w

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.

Note: #EA:B370#LA:B370#

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Contributing Institute(s):

1. Epigenomik (B370)
2. B230 Proteomik von Stammzellen und Krebs (B230)
3. B250 NWG Translationskontrolle und Stoffwechsel (B250)
4. DKTK Koordinierungsstelle Tübingen (TU01)
5. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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