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Updated: Jul 12, 2025

Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
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Generation of Human Monocyte-derived Dendritic Cells from Whole Blood

Published on: December 24, 2016

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

Ashish Goyal1, Jens Bauer2,3,4, Joschka Hey1,5,6

  • 1Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Nature Communications
|October 23, 2023
PubMed

Insights

Epigenetic therapies can enhance cancer immunotherapy by activating endogenous retroviral elements (ERVs). This study identifies novel ERV-derived neoantigens, showing their potential to trigger anti-cancer T-cell responses in patients.

Area of Science:

  • Oncology
  • Immunology
  • Epigenetics

Background:

  • Cancer immunotherapies targeting neoantigens have transformed cancer treatment.
  • Epigenetic therapies may synergize with immunotherapies by reactivating endogenous retroviral elements (ERVs).

Purpose of the Study:

  • To investigate the potential of epigenetic drugs to induce neoantigens from ERVs.
  • To identify and validate treatment-induced neoantigens for cancer therapy.

Main Methods:

  • Deep RNA sequencing of cancer cell lines treated with DNA methyltransferase inhibitors (DNMTi) and/or Histone deacetylase inhibitors (HDACi).
  • De novo transcriptome assembly to identify ERV-derived novel polyadenylated transcripts (TINPATs).
  • Immunopeptidomics to detect human leukocyte antigen (HLA) presented neoantigens (t-neopeptides).

Main Results:

  • Several thousand ERV-derived TINPATs were identified following epigenetic treatment.
  • 45 spectra-validated t-neopeptides originating from TINPATs were detected.
  • t-neopeptides were confirmed in acute myeloid leukemia (AML) patient samples post-Decitabine treatment.

Conclusions:

  • Epigenetic therapies can generate ERV-derived neoantigens that may elicit anti-cancer T-cell responses.
  • These findings support the use of ERV-derived neoantigens in combined epigenetic and immune therapies for cancer treatment.

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