TY  - JOUR
AU  - Goyal, Ashish
AU  - Bauer, Jens
AU  - Hey, Joschka
AU  - Papageorgiou, Dimitris N
AU  - Stepanova, Ekaterina
AU  - Daskalakis, Michael
AU  - Scheid, Jonas
AU  - Dubbelaar, Marissa
AU  - Klimovich, Boris
AU  - Schwarz, Dominic
AU  - Märklin, Melanie
AU  - Roerden, Malte
AU  - Lin, Yu-Yu
AU  - Ma, Tobias
AU  - Mücke, Oliver
AU  - Rammensee, Hans-Georg
AU  - Lübbert, Michael
AU  - Loayza-Puch, Fabricio
AU  - Krijgsveld, Jeroen
AU  - Walz, Juliane
AU  - Plass, Christoph
TI  - DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2023-02154
SP  - 6731
PY  - 2023
N1  - #EA:B370#LA:B370#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37872136
DO  - DOI:10.1038/s41467-023-42417-w
UR  - https://inrepo02.dkfz.de/record/284956
ER  -