Evidence map›Paper›PMID 25931171›Full record

ArticleGynecologic oncology2015

Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients.

Stefania Bellone, Floriana Centritto, Jonathan Black, Carlton Schwab, Diana English, Emiliano Cocco, Salvatore Lopez, Elena Bonazzoli, Federica Predolini, Francesca Ferrari and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gynecologic oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 81 citations in OpenAlex.

  1. Functions, interactions and prognostic role ofJournal of gynecologic oncology · 2025
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  8. The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  9. Review
  10. Biomarkers of tumor-reactive CD4Journal for immunotherapy of cancer · 2022
    Article
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  13. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Stefania BelloneDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Floriana CentrittoDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Jonathan BlackDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Carlton SchwabDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Diana EnglishDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Emiliano CoccoDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Salvatore LopezDivision of Gynecologic Oncology, University Campus Bio-Medico of Roma, Roma, Italy.
Elena BonazzoliDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Federica PredoliniDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Francesca FerrariDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Dan-Arin SilasiDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Elena RatnerDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Masoud AzodiDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Peter E SchwartzDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Alessandro D SantinDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA. Electronic address: alessandro.santin@yale.edu.
Yale University · USUniversità Campus Bio-Medico · IT

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Integrated genomic analysis of racial disparities in endometrial cancerU01CA176067 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2014 to 2018
$1.7M
CPE Peptide-Based Nanoparticles for the Diagnosis and Therapy of Chemotherapy ResR01CA154460 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2011 to 2015
$1.7M
NCI NIH HHS CA-16359NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA154460NCI NIH HHS R01 CA154460-01NCI NIH HHS U01 CA176067NCI NIH HHS U01 CA176067-01A1
6 · The paper itself

Abstract

objectiveAround 7-10% of endometrial carcinomas are characterized by polymerase-ε-(POLE) exonuclease-domain-mutations, an ultra-mutated-phenotype and a favorable prognosis. It is currently unknown whether POLE ultra-mutated-tumors are more immunogenic when compared to the other groups of endometrial cancers.

methodsWe used autologous-dendritic-cells (DC) pulsed with whole-tumor-extracts to assess the level of CD8+ and CD4+ T-cell-activation induced by POLE-ultramutated (+) and POLE wild-type (-) endometrial cancer cells in vitro. T-lymphocyte-proliferations were evaluated using CFSE and/or ([3H])thymidine-incorporation-assays while the ability to specifically kill autologous-tumor-cells by cytotoxic-T-lymphocyte (CTL) was tested in standard 4-h-(51)Cr-cytotoxicity-assays. In order to correlate cytotoxic activity and proliferation by CD4+ and CD8+ T-lymphocytes, respectively, with a particular lymphoid subset, two-color-flow-cytometric analysis of intracellular-cytokine-expression (IFN-γ vs IL-4) at the single cell level was also performed.

resultsDC-pulsed with tumor extracts were able to induce CTL-responses against autologous-tumor-cells in both POLE (+) and POLE (-) cancer patients (P=0.305). These CD8+ T-cell-populations were cytotoxic against tumor-cells but they did not lyse PHA-stimulated-autologous-lymphocytes or autologous-EBV-transformed-lymphoblastoid-control-cell-lines. In contrast, only POLE (+) tumor-lysate-pulsed-DC were able to induce significant proliferation and high IFN-γ expression (i.e., Th1-cytokine-bias) in autologous in vitro DC-stimulated CD4+ T-cells as well as naïve CD4+ and CD8+ T-cells from patients-peripheral-blood (P<0.05).

conclusionsPOLE ultra-mutated-tumors are significantly more immunogenic when compared to POLE (-) tumors, in particular to the helper arm of the immune system. These data lend support to the hypothesis that the better prognosis of patients with POLE (+) tumors may at least in part be linked to their enhanced immunogenicity.

Indexed as

MutationAdultAgedCD4-Positive T-LymphocytesCell Line, TumorDendritic CellsDNA Polymerase IIEndometrial NeoplasmsFemaleHumansLymphocyte ActivationMiddle AgedPoly-ADP-Ribose Binding ProteinsT-Lymphocytes, CytotoxicDNA Polymerase IIPOLE protein, humanPoly-ADP-Ribose Binding ProteinsEndometrial carcinomaPolymerase εUterine serous papillary cancerWhole exome sequencing

Identifiers

PMID25931171
PMCPMC4469551
OpenAlexW1999528962

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.