ArticleBritish journal of cancer2022
Mutant p53 gain of function mediates cancer immune escape that is counteracted by APR-246.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.Cellular & molecular biology letters · 2026Review
- Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis.bioRxiv : the preprint server for biology · 2026Article
- Identification of an m7G-Related lncRNA Signature for Prognostic Prediction and Immune Landscape Characterization in Early Gastric Cancer.OncoTargets and therapy · 2026Article
- Cell cycle dysregulation: a central hub in colitis-associated colorectal carcinogenesis.Frontiers in immunology · 2026Review
- Diagnostic and Prognostic Implications of FGFR3, TP53 Mutation and Urinary Biomarkers in Urothelial Carcinoma in Pakistani Cohort.Journal of clinical medicine · 2025Article
- Identification of high-risk signatures and therapeutic targets through molecular characterization and immune profiling of TP53-mutant breast cancer.Journal, genetic engineering & biotechnology · 2025Article
- P53 Function Status Correlates With Overall Survival in Patients With Resected Pancreatic Cancer.Journal of surgical oncology · 2025Article
- Correlating p53 immunostaining patterns with somatic TP53 mutation and functional properties of mutant p53 in triple-negative breast cancer.Histopathology · 2025Article
- Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial.NPJ breast cancer · 2025Article
- Unraveling the Guardian: p53's Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies.International journal of molecular sciences · 2024Review
- Predictive value ofThe veterinary quarterly · 2024Article
- Review
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- Genetic Changes in Mastocytes and Their Significance in Mast Cell Tumor Prognosis and Treatment.Genes · 2024Review
- p53 deficient breast cancer cells reprogram preadipocytes toward tumor-protective immunomodulatory cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundp53 mutants contribute to the chronic inflammatory tumour microenvironment (TME). In this study, we address the mechanism of how p53 mutants lead to chronic inflammation in tumours and how to transform it to restore cancer immune surveillance.
methodsOur analysis of RNA-seq data from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) project revealed that mutant p53 (mtp53) cancers correlated with chronic inflammation. We used cell-based assays and a mouse model to discover a novel gain of function of mtp53 and the effect of the mtp53 reactivating compound APR-246 on the anti-tumour immune response.
resultsWe found that tumour samples from patients with breast carcinoma carrying mtp53 showed elevated Interferon (IFN) signalling, Tumour Inflammation Signature (TIS) score and infiltration of CD8+ T cells compared to wild type p53 (wtp53) tumours. We showed that the expression of IFN and immune checkpoints were elevated in tumour cells in a mtp53-dependent manner, suggesting a novel gain of function. Restoration of wt function to mtp53 by APR-246 induced the expression of endogenous retroviruses, IFN signalling and repressed immune checkpoints. Moreover, APR-246 promoted CD4+ T cells infiltration and IFN signalling and prevented CD8+ T cells exhaustion within the TME in vivo.
conclusionsBreast carcinomas with mtp53 displayed enhanced inflammation. APR-246 boosted the interferon response or represses immune checkpoints in p53 mutant tumour cells, and restores cancer immune surveillance in vivo.
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