ArticleThe Journal of clinical investigation2022
Increased p53 expression induced by APR-246 reprograms tumor-associated macrophages to augment immune checkpoint blockade.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 23 citations in OpenAlex.
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Eprenetapopt in combination with Palbociclib exerts synthetic lethality in mantle cell lymphoma.Translational oncology · 2026Article
- Research progress on the biological function and molecular mechanism of GDF-15 in solid malignant tumors.World journal of surgical oncology · 2026Review
- Systematic analysis of the mitophagy scoring system in the prognosis and immunotherapy of HCC patients.Discover oncology · 2026Article
- Pan-cancer analysis identifies FAM111B as a biomarker for immune suppression microenvironment in low-grade gliomas.Translational cancer research · 2026Article
- Characteristics and therapeutic resistance mechanisms of the prostate cancer immune microenvironment: a comprehensive analysis from bench to clinic.Frontiers in pharmacology · 2026Review
- Dynamic tumor microenvironment remodeling in cancer therapy resistance: molecular mechanisms and translational opportunities.Frontiers in cell and developmental biology · 2026Review
- DPEP2 suppresses metastasis via NF-κB-mediated epithelial-mesenchymal transition and M2 polarization in p53-loss non-small cell lung cancer.Cancer cell international · 2025Article
- Immunoregulatory properties of cell free DNA.Cellular and molecular life sciences : CMLS · 2025Article
- Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression.BMC neuroscience · 2025Article
- Tumor microenvironment noise-induced polarization: the main challenge in macrophages' immunotherapy for cancer.Molecular and cellular biochemistry · 2025Review
- Lymphatic-derived oxysterols promote anti-tumor immunity and response to immunotherapy in melanoma.Nature communications · 2025Article
- The Role of P53 in Immune Evasion and Therapeutic Strategies in Hematologic Malignancies.Journal of Cancer · 2025Review
- Inverse correlation between TP53 gene status and PD-L1 protein levels in a melanoma cell model depends on an IRF1/SOX10 regulatory axis.Cellular & molecular biology letters · 2024Article
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- p53 at the crossroads of tumor immunity.Nature cancer · 2024Review
- Engineered Immunologic Niche Monitors Checkpoint Blockade Response and Probes Mechanisms of Resistance.Immunomedicine · 2024Article
- Review
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
Corrections and comments
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Authors and funding
27 authors at 3 institutions in 1 country.
Funding
Abstract
In addition to playing a major role in tumor cell biology, p53 generates a microenvironment that promotes antitumor immune surveillance via tumor-associated macrophages. We examined whether increasing p53 signaling in the tumor microenvironment influences antitumor T cell immunity. Our findings indicate that increased p53 signaling induced either pharmacologically with APR-246 (eprenetapopt) or in p53-overexpressing transgenic mice can disinhibit antitumor T cell immunity and augment the efficacy of immune checkpoint blockade. We demonstrated that increased p53 expression in tumor-associated macrophages induces canonical p53-associated functions such as senescence and activation of a p53-dependent senescence-associated secretory phenotype. This was linked with decreased expression of proteins associated with M2 polarization by tumor-associated macrophages. Our preclinical data led to the development of a clinical trial in patients with solid tumors combining APR-246 with pembrolizumab. Biospecimens from select patients participating in this ongoing trial showed that there was a suppression of M2-polarized myeloid cells and increase in T cell proliferation with therapy in those who responded to the therapy. Our findings, based on both genetic and a small molecule-based pharmacological approach, suggest that increasing p53 expression in tumor-associated macrophages reprograms the tumor microenvironment to augment the response to immune checkpoint blockade.
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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.