ArticleCancer discovery2021
Pharmacologic Activation of p53 Triggers Viral Mimicry Response Thereby Abolishing Tumor Immune Evasion and Promoting Antitumor Immunity.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.Nature communications · 2026Article
- The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Inactivation of CDKN2AARF Promotes p53-Independent Remodeling of the PDAC Tumor Microenvironment.Cancer research · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- PARP1 inhibition in naïve mouse embryonic stem cells induces viral mimicry.Nucleic acids research · 2026Article
- In vivo CRISPR screens identify CBX4 as an epigenetic regulator for cancer immunotherapy.The Journal of clinical investigation · 2026Article
- Transient p53/p21 activation selectively protects healthy human hair follicles and their stem cells from chemotherapy.The Journal of clinical investigation · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.Cellular & molecular biology letters · 2026Review
- MORC2 promotes acute myeloid leukemia by silencing LINE-1 retrotransposon.Functional & integrative genomics · 2026Article
- Viral mimicry acts as a tumor suppressor in colitis.Nature communications · 2026Article
- CDK10 suppresses nucleic acid sensors-mediated antitumor immunity.Nature cancer · 2026Article
- LSD1 Inhibition Induces MHC-I and Dendritic Cell Activation to Promote Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Inhibition of LDHA promotes GSDME-dependent pyroptosis by activating RIG-I-like receptor signaling.Apoptosis : an international journal on programmed cell death · 2026Article
- Epigenetic Modulators and Immunotherapy in Malignant Melanoma.Oncology research · 2026Review
- Endogenous retroviruses in aging and cancer: from genomic defense to oncogenic activation.Mobile DNA · 2025Review
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- Analysis of human endogenous retrovirus in hepatocellular carcinomas using HERV-Fcount.BMC microbiology · 2025Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The repression of repetitive elements is an important facet of p53's function as a guardian of the genome. Paradoxically, we found that p53 activated by MDM2 inhibitors induced the expression of endogenous retroviruses (ERV) via increased occupancy on ERV promoters and inhibition of two major ERV repressors, histone demethylase LSD1 and DNA methyltransferase DNMT1. Double-stranded RNA stress caused by ERVs triggered type I/III interferon expression and antigen processing and presentation. Pharmacologic activation of p53 in vivo unleashed the IFN program, promoted T-cell infiltration, and significantly enhanced the efficacy of checkpoint therapy in an allograft tumor model. Furthermore, the MDM2 inhibitor ALRN-6924 induced a viral mimicry pathway and tumor inflammation signature genes in patients with melanoma. Our results identify ERV expression as the central mechanism whereby p53 induction overcomes tumor immune evasion and transforms tumor microenvironment to a favorable phenotype, providing a rationale for the synergy of MDM2 inhibitors and immunotherapy. SIGNIFICANCE: We found that p53 activated by MDM2 inhibitors induced the expression of ERVs, in part via epigenetic factors LSD1 and DNMT1. Induction of IFN response caused by ERV derepression upon p53-targeting therapies provides a possibility to overcome resistance to immune checkpoint blockade and potentially transform "cold" tumors into "hot." This article is highlighted in the In This Issue feature, p. 2945.
Indexed as
Identifiers
What OpenQuestion holds
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.