The DOI matches its Crossref record; 93 of the 94 references it cites were found in a registry or an index.
Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses
Open accessAbstract
We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway. In ovarian cancer (OC), DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a type I interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS reduces this response 2-fold and blocking interferon beta or its receptor abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes accompanies the response and ERV overexpression activates the response. Basal levels of ERV and viral defense gene expression significantly correlate in primary OC and the latter signature separates primary samples for multiple tumor types from The Cancer Genome Atlas into low versus high expression groups. In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The IFN-I response could also expose the tumor cells to surveillance by the immune system96, 97.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [97]
The cited source says what the claim attributes to it.
In the citing paper
“multiple studies have shown that DNA demethylating agents among other epigenetic modulators can induce a type I IFN response in cancer cells through the de-repression of endogenous retroviruses (ERVs) and activation of the MDA5-MAVS pathway38–40.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [38]
The cited source says what the claim attributes to it.
In the citing paper
“DAC treatment could induce expression of retrotransposons normally silenced by DNA methylation, which could also augment tumor immunogenicity10–14,99.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [12]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“inactivated typical enhancers were associated with collagen fibril organization and chemotaxis GO terms and were enriched for binding motifs of immune-related TFs, including STAT1 (Fig. 2a, b)12,13.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [12]
Experimental — accuracy not yet measuredIn the citing paper
“inhibiting EZH2 activity can either positively or negatively influence tumour-specific immune responses by modulating both tumour immunogenicity and the function of infiltrating T-cells, NK-cells and macrophages 196 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [196]
In the citing paper
“derepression of endogenous retroviral elements coupled to robust type I and type III IFN signaling”
From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Chiappinelli et al., 2015
In the citing paper
“Certainly, this dual epigenetic targeting may influence additional antiproliferative mechanisms and further enhance antitumor surveillance by the immune system (Chiappinelli et al., 2015).”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Chiappinelli et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Self-citationThe blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Self-citationSafety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Self-citationPD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Self-citationSafety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
Self-citationMutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
Self-citationCancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011) · Science · doi:10.1126/science.1203486 · Cited by 6,474
ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking
Wilkerson, M. D., & Hayes, D. N. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq170 · Cited by 5,645
Flagged first, then by citations
1 of the 94 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 1,001–1,003 of 1,003
Dumetier, B., Sauter, C., Hajmirza, A., Pernon, B., Aucagne, R., Fournier, C., Row, C., Guidez, F., Rossi, C., Lepage, C., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10123101 · Cited by 9
A multiomics approach reveals RNA dynamics promote cellular sensitivity to DNA hypomethylation
Ge, A. Y., Arab, A., Dai, R., Navickas, A., Fish, L., Garcia, K., Asgharian, H., Goudreau, J., Lee, S., Keenan, K., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-77314-9 · Cited by 4
Cheng, C. C. Y., Cheung, M. F., Lee, A. Y., Wu, Q., Chow, S. H.-C., Ang, J. Y. J., Riquelme Medina, I., Lo, G., Wu, H., Yang, W., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09154-w · Cited by 3
Metadata
- Authors
- Chiappinelli, K. B., Strissel, P. L., Desrichard, A., Li, H., Henke, C., Akman, B., Hein, A., Rote, N. S., Cope, L. M., Snyder, A., Makarov, V., Buhu, S., Slamon, D. J., Wolchok, J. D., Pardoll, D. M., Beckmann, M. W., Zahnow, C. A., Merghoub, T., Chan, T. A., Baylin, S. B., & Strick, R.
- Affiliations
- Johns Hopkins University (US)
- Universitätsklinikum Erlangen (DE)
- Memorial Sloan Kettering Cancer Center (US)
- Case Western Reserve University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Baylin, Stephen B.
- Strick, Reiner
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 162
- Issue
- 5
- Pages
- 974-986
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4556003
- OpenAlex
- W1953890763
- Cited by
- 2,022
- References
- 94
- Citations by year
- 2026: 193 · 2025: 188 · 2024: 211 · 2023: 209 · 2022: 225 · 2021: 250 · 2020: 184 · 2019: 163 · 2018: 161 · 2017: 133 · 2016: 93 · 2015: 10
- FWCI
- 65.10
- Type
- journal article
- Language
- en
- Update notices
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P50CA058184, CA058184, F32CA183214, P30CA008748)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- hypomethylating agents, DNA methylation, type I interferon response, double-stranded RNA sensing, endogenous retroviruses, ovarian cancer, melanoma, TLR3, MAVS, interferon-beta, apoptosis, immune checkpoint therapy, CTLA-4, tumor immune microenvironment, epigenetic reprogramming
- MeSH terms
- Animals, Azacitidine, Female, Humans, Immunotherapy, Interferon Type I, Lung Neoplasms, Melanoma, Mice, Inbred C57BL, Ovarian Neoplasms, RNA, Double-Stranded, DNA Modification Methylases, DNA Methylation, Endogenous Retroviruses, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
