ArticleNature genetics2022
Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07695311 (Precision Analysis of Fusion Genes in Ewing Sarcoma), which is not on this map. Cited by 54 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.
Precision Analysis of Fusion Genes in Ewing Sarcoma (ES) and Desmoplastic Small Round Cell Tumor (DSRCT), Then EWSR1 (Ewing Sarcoma Gene Breakpoint Region 1 Gene) Immunotherapy Without or With Anti-CTLA-4 (Botensilimab) and Anti-PD1 (Balstilimab)
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update.Cancer communications (London, England) · 2025Guideline
- A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta (POLE/POLD1) mutation.Signal transduction and targeted therapy · 2024Trial
- Tumour-agnostic immunotherapy: aligning biological rationale, biomarker precision, and real-world implementation.EClinicalMedicine · 2026Review
- Deficiency in POLE Exonuclease Causes Synthetic Lethality in Highly Aneuploid Cancer Cells.Cancer research · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Case Report: Tumor regression and neurological recovery in paraplegia from POLD1-mutated hepatocellular carcinoma treated with targeted immunotherapy and electroacupuncture.Frontiers in immunology · 2026Article
- Innate immunity in tumour immunoediting and immunosurveillance.The EMBO journal · 2026Review
- Article
- Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations.International journal of molecular sciences · 2025Article
- Of Context, Quality, and Complexity: Fine-Combing Tumor Mutational Burden in Immunotherapy-Treated Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Updates of CSCO guidelines for colorectal cancer version 2025.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Unveiling ctDNA Response: Immune Checkpoint Blockade Therapy in a Patient with POLE Mutation-Associated Early-Onset Colon Cancer.Current oncology (Toronto, Ont.) · 2025Article
- AlphaMissense for Identifying Pathogenic Missense Mutations in DNA Damage Repair Genes in Cancer.JCO precision oncology · 2025Article
- The cold immunological landscape of ATM-deficient cancers.Journal for immunotherapy of cancer · 2025Article
- Navigating established and emerging biomarkers for immune checkpoint inhibitor therapy.Cancer cell · 2025Review
- [The role of immunosurveillance and immunoediting in hereditary cancer predisposition syndromes].Magyar onkologia · 2025Review
- Immune Checkpoint Blockade Delays Cancer Development and Extends Survival in DNA Polymerase Mutator Syndromes.Cancer research · 2025Article
- Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape.eLife · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 4 institutions in 1 country.
Funding
Abstract
Defects in pathways governing genomic fidelity have been linked to improved response to immune checkpoint blockade therapy (ICB). Pathogenic POLE/POLD1 mutations can cause hypermutation, yet how diverse mutations in POLE/POLD1 influence antitumor immunity following ICB is unclear. Here, we comprehensively determined the effect of POLE/POLD1 mutations in ICB and elucidated the mechanistic impact of these mutations on tumor immunity. Murine syngeneic tumors harboring Pole/Pold1 functional mutations displayed enhanced antitumor immunity and were sensitive to ICB. Patients with POLE/POLD1 mutated tumors harboring telltale mutational signatures respond better to ICB than patients harboring wild-type or signature-negative tumors. A mutant POLE/D1 function-associated signature-based model outperformed several traditional approaches for identifying POLE/POLD1 mutated patients that benefit from ICB. Strikingly, the spectrum of mutational signatures correlates with the biochemical features of neoantigens. Alterations that cause POLE/POLD1 function-associated signatures generate T cell receptor (TCR)-contact residues with increased hydrophobicity, potentially facilitating T cell recognition. Altogether, the functional landscapes of POLE/POLD1 mutations shape immunotherapy efficacy.
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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.