ArticleCancer immunology research2022
PBRM1 Inactivation Promotes Upregulation of Human Endogenous Retroviruses in a HIF-Dependent Manner.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 23 citations in OpenAlex.
- Distinct endogenous retroviruses are expressed in mutational subtypes of clear cell renal cell carcinoma and are linked to improved clinical outcomes.Cell reports · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Essential genetic mutations impair DNA damage repair and modulate tumor immune microenvironment in ccRCC.MedScience · 2026Review
- Retroviral Remnants in the Human Genome: Classification, Integration and Regulation.Molecular diagnosis & therapy · 2026Review
- The expression, regulation, and function of human endogenous retroviruses in genitourinary cancers.Cell death discovery · 2025Review
- Immunological features of clear-cell renal-cell carcinoma and resistance to immune checkpoint inhibitors.Nature reviews. Nephrology · 2025Review
- Coordinated expression of retained introns and poison exons in renal cell carcinoma.Cell reports · 2025Article
- HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy.Cell · 2025Article
- Reducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATAC.bioRxiv : the preprint server for biology · 2025Article
- Review
- Current perspective on the impact of endogenous retroviruses in clear cell renal cell carcinoma.Kidney cancer journal : official journal of the Kidney Cancer Association · 2023Article
- von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology.Hematology/oncology clinics of North America · 2023Review
- Essential role of bromodomain proteins in renal cell carcinoma (Review).Molecular medicine reports · 2023Review
- Immunogenicity in renal cell carcinoma: shifting focus to alternative sources of tumour-specific antigens.Nature reviews. Nephrology · 2023Review
- Viewing RCC with a DNA Methylation Lens ENHANCES Understanding of ICI Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape.Genome medicine · 2022Article
- The convergence of tumor suppressors on the type I interferon pathway in clear cell renal cell carcinoma and its therapeutic implications.American journal of physiology. Cell physiology · 2022Review
- The cuproptosis-associated 13 gene signature as a robust predictor for outcome and response to immune- and targeted-therapies in clear cell renal cell carcinoma.Frontiers in immunology · 2022Article
- An Immune-Related Long Noncoding RNA Pair as a New Biomarker to Predict the Prognosis of Patients in Breast Cancer.Frontiers in genetics · 2022Article
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7 authors at 1 institution in 1 country.
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Abstract
Clear cell renal cell carcinoma (ccRCC) is considered an immunotherapy-responsive disease; however, the reasons for this remain unclear. Studies have variably implicated PBRM1 mutations as a predictive biomarker of immune checkpoint blockade (ICB) response, and separate studies demonstrate that expression of human endogenous retroviruses (hERV) might be an important class of tumor-associated antigens. We sought to understand whether specific mutations were associated with hERV expression. Two large, annotated genomic datasets, TCGA KIRC and IMmotion150, were used to correlate mutations and hERV expression. PBRM1 mutations were consistently associated with increased hERV expression in primary tumors. In vitro silencing of PBRM1, HIF1A, and HIF2A followed by RNA sequencing was performed in UMRC2 cells, confirming that PBRM1 regulates hERVs in a HIF1α- and HIF2α-dependent manner and that hERVs of the HERVERI superfamily are enriched in PBRM1-regulated hERVs. Our results uncover a role for PBRM1 in the negative regulation of hERVs in ccRCC. Moreover, the HIF-dependent nature of hERV expression explains the previously reported ccRCC-specific clinical associations of PBRM1-mutant ccRCC with both a good prognosis as well as improved clinical outcomes to ICB. See related Spotlight by Labaki et al., p. 274.
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