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HIF Regulates Multiple Translated Endogenous Retroviruses: Implications for Cancer Immunotherapy [PRO-seq]

GSE253324 Homo sapiens Expression profiling by high throughput sequencing; Other 6 samples Submitted 2025/02/20 Platform GPL24676
Summary
Clear cell renal cell carcinoma (ccRCC), despite having a low mutational burden, is considered immunogenic because it occasionally undergoes spontaneous regressions and often responds to immunotherapies. The signature lesion in ccRCC is inactivation of the VHL tumor suppressor gene and consequent upregulation of the HIF transcription factor. An earlier case report described a ccRCC patient who was cured by an allogeneic stem cell transplant and later found to have donor-derived T cells that recognized a ccRCC-specific peptide encoded by a HIF-responsive endogenous retrovirus (ERVE-4). We report that ERVE-4 is one of many ERVs that are induced by HIF, translated into HLA-bound peptides in ccRCCs, and capable of generating antigen-specific T cell responses. Moreover, ERV expression can be induced in non-ccRCC tumors with clinical-grade HIF stabilizers. These findings have implications for leveraging ERVs for cancer immunotherapy.
Published in
HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy
Jiang Q, Braun DA, Clauser KR et al. · Cell 2025 · PMID 40023154 · doi:10.1016/j.cell.2025.01.046
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Also filed as BioProject PRJNA1065292 and SRA study SRP483946. Searching any of these in the dataset finder brings you back here.

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