| Autor: |
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, Christoph Plass |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-19 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-42417-w |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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