%0 Journal Article
%A Goyal, Ashish
%A Bauer, Jens
%A Hey, Joschka
%A Papageorgiou, Dimitris N
%A Stepanova, Ekaterina
%A Daskalakis, Michael
%A Scheid, Jonas
%A Dubbelaar, Marissa
%A Klimovich, Boris
%A Schwarz, Dominic
%A Märklin, Melanie
%A Roerden, Malte
%A Lin, Yu-Yu
%A Ma, Tobias
%A Mücke, Oliver
%A Rammensee, Hans-Georg
%A Lübbert, Michael
%A Loayza-Puch, Fabricio
%A Krijgsveld, Jeroen
%A Walz, Juliane
%A Plass, Christoph
%T DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts.
%J Nature Communications
%V 14
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2023-02154
%P 6731
%D 2023
%Z #EA:B370#LA:B370#
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37872136
%R 10.1038/s41467-023-42417-w
%U https://inrepo02.dkfz.de/record/284956