ArticleCancer research2022
SETDB1 Restrains Endogenous Retrovirus Expression and Antitumor Immunity during Radiotherapy.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 39 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Article
- Tumor cell-intrinsic TET3 restrains type I interferon signaling and anti-tumor immunity.Science China. Life sciences · 2026Article
- The HIV-1 restriction factor RPRD2 does not inhibit transcription of HIV-1 or endogenous retroelements.bioRxiv : the preprint server for biology · 2026Article
- Histone H3.3 ensures cell proliferation and genomic stability during myeloid cell development.iScience · 2026Article
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- METTL3 Methylation Induces Decay of Endogenous Retroelement Transcripts to Promote Tumor Immune Evasion.Cancer research · 2026Article
- mNature communications · 2026Article
- Overcoming immunotherapy barriers in pediatric brain tumors: epigenetic strategies.Frontiers in oncology · 2026Review
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- A noncanonical cytoplasmic role for BUB1 in restraining DNA damage-induced dsRNA accumulation and sensing within stress granules.Science immunology · 2025Article
- Metabolism and Immune Suppressive Response in Liver Cancer.Biomedicines · 2025Review
- Combination Therapy Approaches to Enhance the Efficacy of ERV-Targeting Vaccines in Cancer.Cancer immunology research · 2025Review
- Targeting SETDB1 in cancer and immune regulation: Potential therapeutic strategies in cancer.The Kaohsiung journal of medical sciences · 2025Review
- Identification and clinical implications of endogenous retrovirus elements suppressed by SETDB1 in hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2025Article
- SETDB1 amplification in osteosarcomas: Insights from its role in healthy tissues and other cancer types.Oncotarget · 2025Review
- Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy.International journal of biological sciences · 2025Review
- Article
- Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges.The Journal of clinical investigation · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The type I interferon response plays a pivotal role in promoting antitumor immune activity in response to radiotherapy. The identification of approaches to boost the radiation-induced type I interferon response could help improve the efficacy of radiotherapy. Here we show that the histone methyltransferase SETDB1 is a potent suppressor of radiation-induced endogenous retrovirus expression. SETDB1 inhibition significantly enhanced the efficacy of radiotherapy by promoting radiation-induced viral mimicry to upregulate type I interferons. SETDB1 expression correlated with radiotherapy efficacy in human non-small cell carcinoma and melanoma patients. In a murine tumor model, genetic deletion of Setdb1 significantly enhanced radiotherapy efficacy, and Setdb1-deficient tumors had enhanced intratumoral lymphocyte infiltration, an observation confirmed in human cancer samples. Setdb1 deficiency led to increased basal and radiation-induced endogenous retrovirus (ERV) expression, enhanced MDA5/MAVS signaling, and upregulated type I interferons, which were essential for SETDB1 deficiency-induced radiosensitization. Taken together, these data suggest that inhibition of SETDB1 is a promising approach to enhance cancer radiotherapy efficacy by promoting radiation-induced viral mimicry and antitumor immunity through ERV induction. SIGNIFICANCE: The identification of the SETDB1-mediated suppression of radiotherapy-induced viral mimicry reveals SETDB1 inhibition as a potential approach to sensitize tumors to radiotherapy by enhancing the type I interferon response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.