Evidence map›Paper›PMID 23118856›Full record

ArticlePloS one2012

Regulatory T-cells and associated pathways in metastatic renal cell carcinoma (mRCC) patients undergoing DC-vaccination and cytokine-therapy.

Adrian Schwarzer, Benita Wolf, Jan L Fisher, Thomas Schwaab, Sven Olek, Udo Baron, Craig R Tomlinson, John D Seigne, Nancy A Crosby, Jiang Gui and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. KIR2DL2/DL3+NKs and Helios+Tregs in Peripheral Blood Predict Nivolumab Response in Patients with Metastatic Renal Cell Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  3. Biomarkers in renal cell carcinoma and their targeted therapies: a review.Exploration of targeted anti-tumor therapy · 2023
    Review
  4. The Role of DNA Methylation in Renal Cell Carcinoma.Molecular diagnosis & therapy · 2018
    Review
  5. Article
  6. Article
  7. Review
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Adrian SchwarzerMedical Oncology Immunotherapy Group, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Benita Wolf
Jan L Fisher
Thomas Schwaab
Sven Olek
Udo Baron
Craig R Tomlinson
John D Seigne
Nancy A Crosby
Jiang Gui
Thomas H Hampton
Camilo E Fadul
John A Heaney
Marc S Ernstoff
Dartmouth College · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
VARIATION IN BIOACCUMULATION AND BIOMAGNIFICATION OF METALS IN NORTHERN US LAKESP42ES007373 · NIEHS · DARTMOUTH COLLEGE · PI STANTON, BRUCE A. · 1995 to 2019
$52.0M
VASCULAR LEUKOCYTES: BASIC IMMUNOBIOLOGY AND FUNCTIONAL PLASTICITYP20RR016437 · NCRR · DARTMOUTH COLLEGE · PI ERNSTOFF, MARC S · 2001 to 2010
$24.3M
TRANSLATIONAL RESEARCH COREP30GM106394 · NIGMS · DARTMOUTH COLLEGE · PI MADDEN, DEAN R · 2013 to 2017
$6.1M
Immunotherapy for Renal Cell CarcinomaR01CA095648 · NCI · DARTMOUTH COLLEGE · PI ERNSTOFF, MARC S · 2003 to 2010
$2.3M
Cellular and Molecular Mechanisms of Lung DiseaseP20GM103413 · NIGMS · DARTMOUTH COLLEGE · PI STANTON, BRUCE A. · 2012 to 2012
$2.1M
NCI NIH HHS P30 CA023108NCI NIH HHS P30CA023108NCI NIH HHS R01 CA095648NCRR NIH HHS P20 RR016437NCRR NIH HHS P20RR016437NIEHS NIH HHS P42 ES007373NIEHS NIH HHS P42ES007373NIGMS NIH HHS P20 GM103413NIGMS NIH HHS P20GM103413NIGMS NIH HHS P30 GM106394
6 · The paper itself

Abstract

purposeTo evaluate CD4(+)CD25(+)FOXP3(+) T regulatory cells (T(REG)) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating T(REG) combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis.

designEighteen patients with mRCC and twelve volunteers (controls) were available for analysis. T(REG) phenotype was examined using flow cytometry (FCM). T(REG) were also quantified by analyzing the epigenetic status of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of the PBL was hybridized to Affymetrix GeneChip Human Gene 1.0 ST Arrays and the gene signatures were explored using pathway analysis.

resultsWe observed higher numbers of T(REG) in pre-treatment PBL of mRCC patients compared to controls. A significant increase in T(REG) was detected in all mRCC patients after the two cycles of immunotherapy. The expansion of T(REG) was significantly higher in non-responders than in responding patients. Methylation specific PCR confirmed the FCM data and circumvented the variability and subjectivity of the FCM method. Gene Set Enrichment Analysis (GSEA) of the microarray data showed significant enrichment of FOXP3 target genes, CTLA-4 and TGF-ß associated pathways in the patient cohort.

conclusionImmune monitoring of the peripheral blood and tumor tissue is important for a wide range of diseases and treatment strategies. Adoption of methodology for quantifying T(REG) with the least variability and subjectivity will enhance the ability to compare and interpret findings across studies.

Indexed as

Carcinoma, Renal CellForkhead Transcription FactorsImmunotherapyT-Lymphocytes, RegulatoryCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCTLA-4 AntigenDNA MethylationFemaleFlow CytometryGene Expression ProfilingHumansInterleukin-2MaleMetabolic Networks and PathwaysCTLA-4 AntigenForkhead Transcription FactorsFOXP3 protein, humanInterleukin-2Transforming Growth Factor beta

Identifiers

PMID23118856
PMCPMC3485261
OpenAlexW2091334680

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.