生物
表观遗传学
组蛋白脱乙酰基酶
癌症研究
组蛋白脱乙酰酶抑制剂
DNA甲基转移酶
DNA甲基化
甲基转移酶
分子生物学
组蛋白
DNA
甲基化
基因表达
遗传学
基因
作者
Ashish Goyal,Jens Bauer,Joschka Hey,Dimitris Papageorgiou,Ekaterina Stepanova,Michael Daskalakis,Jonas Scheid,Marissa L. 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
标识
DOI:10.1038/s41467-023-42417-w
摘要
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.
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