ArticleJournal for immunotherapy of cancer2025
HERV-derived epitopes represent new targets for T-cell-based immunotherapies in ovarian cancer.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed.
- Receptor-defined targeting of a genomically unique melanoma-enriched noncanonical antigen.Signal transduction and targeted therapy · 2026Article
- Review
- Review
- CDK9 Inhibition with enitociclib reveals influence on HERV and LINE RNA abundances in whole blood, T-, and B-Cell lines.BMC medical genomics · 2026Article
- Activation of endogenous retroviruses in tumor cells and their immunomodulatory mechanisms: from molecular basis to clinical translation.Frontiers in oncology · 2026Review
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25 authors.
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Abstract
backgroundOvarian cancer represents the most lethal gynecological cancer with poor response to checkpoint inhibitors. Human endogenous retroviruses (HERVs) are aberrantly expressed by tumor cells and may represent a source of shared T-cell epitopes for cancer immunotherapy regardless of the tumor mutational burden.
methodsA transcriptomic analysis based on RNA sequencing was developed to quantify the expression of HERV-K sequences containing the selected epitopes. The presence of HERV-K/HML-2 Gag antigen was then assessed by immunohistochemistry (IHC) on tumor microarrays from ovarian cancer samples and normal ovarian tissues. A specific immunopeptidomics approach was developed to detect epitopes on human leukocyte antigens (HLA) molecules. Epitope-specific CD8
resultsEpitope-containing HERV transcripts were significantly higher in ovarian cancers compared with normal tissues. The presence of the HERV-K/HML-2 Gag antigen was confirmed by IHC in 20/40 (50%) ovarian cancers while no Gag expression was found in normal ovarian tissue samples. Immunopeptidomics analysis revealed the presence of epitopes on HLA molecules on the surface of ovarian tumor cell lines but not on normal primary cells from critical tissues. Low percentages of HERV-specific T cells were detected among tumor-infiltrating lymphocytes from ovarian cancers. Furthermore, in vitro stimulation of patient T cells induced functional epitope-specific T cells, confirming the immunogenicity of these epitopes in patients with ovarian cancer. In vitro, HERV-specific T cells specifically killed ovarian cancer cells in an HLA class I-restricted manner while sparing normal HLA-A2-positive primary cells derived from critical tissues. Epitope-specific CD8
conclusionThese results provide the preclinical rationale for developing T-cell-based approaches against HERV-K-derived epitopes in ovarian cancer.
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