ArticleCancer discovery2022
PD-1 Blockade in Solid Tumors with Defects in Polymerase Epsilon.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 3 of them syntheses 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
51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Efficacy of dostarlimab in recurrent or advanced mismatch Repair-Deficient endometrial Cancer as a Single-Agent therapy: A systematic review and Meta-Analysis.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2025Pooled it
- The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update.Cancer communications (London, England) · 2025Guideline
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer.Journal for immunotherapy of cancer · 2023Guideline
- 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
- Review
- Targeting DNA Polymerase Epsilon Induces Tumor Clearance and Activates an NF-κB-Mediated Inflammatory Response in Triple-Negative Breast Cancer.Cancer research · 2026Article
- Rarity within rarity: complete response to chemoimmunotherapy in a patient with polymerase epsilon (POLE)-mutated locally advanced jejunal carcinoma.The oncologist · 2026Article
- Review
- Acquired High Tumor Mutational Burden and Activity of Immunotherapy after Targeted Therapy in Microsatellite Stable Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Prognostic Impact of Blood Tumor Mutational Burden in pMMR/MSS Metastatic Colorectal Cancer Assessed by FoundationOneCancers · 2026Article
- The clinical landscape of POLE-mutant colorectal cancer: a retrospective analysis of real-world outcome.BMC medicine · 2026Article
- Prognosis and treatment response stratification according to loss of proofreading (LOP)Journal for immunotherapy of cancer · 2025Article
- Targeted therapy in patients with genetic tumor syndromes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- XPO1 R749Q Mutations Co-occur with POLE Mutations in Cancer and Can Be Targeted to Overcome Chemoresistance.Cancer research · 2025Article
- Identification of clusters related to programmed cell death and potential prognostic biomarkers for immunotherapy response in endometrial cancer.Scientific reports · 2025Article
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- Programmed Cell Death Ligand as a Biomarker for Response to Immunotherapy: Contribution of Mass Spectrometry-Based Analysis.Cancers · 2025Review
- Analysis of Shared Variants between Cancer Biospecimens.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Pancreatic Ductal Adenocarcinoma with Medullary Features and a Complete Pathological Response After Neoadjuvant FOLFIRINOX: A Case Report and Literature Review.Journal of gastrointestinal cancer · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
56 authors at 20 institutions in 2 countries.
Funding
Abstract
Missense mutations in the polymerase epsilon (POLE) gene have been reported to generate proofreading defects resulting in an ultramutated genome and to sensitize tumors to checkpoint blockade immunotherapy. However, many POLE-mutated tumors do not respond to such treatment. To better understand the link between POLE mutation variants and response to immunotherapy, we prospectively assessed the efficacy of nivolumab in a multicenter clinical trial in patients bearing advanced mismatch repair-proficient POLE-mutated solid tumors. We found that only tumors harboring selective POLE pathogenic mutations in the DNA binding or catalytic site of the exonuclease domain presented high mutational burden with a specific single-base substitution signature, high T-cell infiltrates, and a high response rate to anti-PD-1 monotherapy. This study illustrates how specific DNA repair defects sensitize to immunotherapy. POLE proofreading deficiency represents a novel agnostic biomarker for response to PD-1 checkpoint blockade therapy. SIGNIFICANCE: POLE proofreading deficiency leads to high tumor mutational burden with high tumor-infiltrating lymphocytes and predicts anti-PD-1 efficacy in mismatch repair-proficient tumors. Conversely, tumors harboring POLE mutations not affecting proofreading derived no benefit from PD-1 blockade. POLE proofreading deficiency is a new tissue-agnostic biomarker for cancer immunotherapy. This article is highlighted in the In This Issue feature, p. 1397.
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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.