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DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE209777 | GEO | 2023/08/22

REPOSITORIES: GEO

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DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

Project description:Immunotherapies targeting cancer-specific immunogenic neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies could synergize with immunotherapies, mediating the de-repression of endogenous retroviral element (ERV)-encoded promoters, and the initiation of transcription. Here we use RNA sequencing from cancer cells treated with DNMT and/or HDAC inhibitors, to assemble a de novo transcriptome and identified 3,023 ERV-derived, treatment-induced novel polA+ transcripts (TINPATs), encoding for 61,426 novel open reading frames. We further demonstrate, using human leukocyte antigen immunopeptidomics, the existence of treatment-induced neoepitopes (t-neoepitopes) derived from TINPATs. We demonstrated the potential of the identified t-neoepitopes to elicit an immunogenic T-cell response and cancer cell killing. The presence of t-neoepitopes was further verified in AML patient samples 48 h and /96 h after in vivo treatment with the DNMT inhibitor Decitabine. Our findings highlight a novel mechanism of ERV-derived neoantigens in epigenetic and immune therapies.

2023-09-13 | PXD035748 | Pride

DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

Project description:Immunotherapies targeting cancer-specific neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies synergize with immunotherapies, mediated bythe 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 inhibitors (DNMTi) and/or Histone deacetylase transferase inhibitors (HDACi), to assemble a de novo transcriptome and identified 3,023 ERV-derived, treatment-induced novel polyadenylated transcripts (TINPATs), encoding for 61,426 open reading frames. Using Immunopeptidomics, we further demonstrate the human leukocyte antigen (HLA) presentation of treatment-induced neoepitopes (t-neoepitopes) derived from TINPATs. We illustrate the potential of the identified t-neoepitopes to elicit a T-cell response and cancer cell killing. The presence of t-neoepitopes was further verified in AML patient samples 48/96 h after in vivo treatment with the DNMT inhibitor Decitabine. Our findings highlight a novel mechanism of ERV-derived neoantigens in epigenetic and immune therapies.

2023-08-18 | PXD035750 | Pride

DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts [Ribo-Seq]

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DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts [RNA-Seq]

Project description:To investigate the effect of Decitabine and SB939 treatment on the expression of endoretroviral elements. We treated 9 cell lines with DMSO, Decitabine, SB939 or a combination of Decitabine and SB939 and performed RNA-seq. This data was used to generate a denovo transcriptome assembly to identify novel mRNAs expressed from endoretroviral elements.

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