Evidence map›Paper›PMID 19577568›Full record

ArticleGastroenterology2009

Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma.

Frank A Sinicrope, Rafaela L Rego, Stephen M Ansell, Keith L Knutson, Nathan R Foster, Daniel J Sargent

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 8 pooled it
10.3field-weighted citation impact, top 1% 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

189 citing papers in PubMed, 8 syntheses or guidelines pooled it, 326 citations in OpenAlex.

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  16. A laminin α4-CD8Oncoimmunology · 2025
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129 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 3 countries.

Frank A SinicropeMiles and Shirley Fiterman Digestive Disease Center, Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. sinicrope.frank@mayo.edu
Rafaela L Rego
Stephen M Ansell
Keith L Knutson
Nathan R Foster
Daniel J Sargent
Mayo Clinic in Arizona · USMayo Clinic · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
Clinical Significance of Apoptosis in Colon CancerR01CA104683 · NCI · MAYO CLINIC ROCHESTER · PI SINICROPE, FRANK A. · 2003 to 2006
$1.0M
NCI NIH HHS CA104683-02NCI NIH HHS N01 CA015083NCI NIH HHS P30 CA015083NCI NIH HHS R01 CA104683
6 · The paper itself

Abstract

BACKGROUND &

aimsRegulatory T cells (Tregs) express the forkhead box transcription factor (FoxP3) and suppress the antitumor immune response. We investigated whether the intratumoral densities of FoxP3(+) and effector CD3(+) lymphocytes are associated with prognosis of patients with colon cancer.

methodsFoxP3 and CD3 expression and location were determined in stage II and III colon carcinomas (n = 160) and normal mucosa (n = 25) by immunohistochemistry; CD4 and FoxP3 were localized by dual immunofluorescence microscopy. T-cell markers were compared with pathological variables, DNA mismatch repair status, and patient survival using Cox proportional hazards models.

resultsFoxP3(+) and CD3(+) T-cell densities were increased in carcinomas compared with autologous normal mucosa (P < .0001). An increase in intraepithelial FoxP3(+) cells was associated with poor tumor differentiation (P = .038), female sex (P = .028), and advanced patient age (P = .042). FoxP3(+) cell density was not prognostic, yet patients with tumors with reduced intraepithelial CD3(+) T-cell densities had reduced disease-free survival (DFS) rates (hazard ratio [HR], 1.87 [95% confidence interval, 1.10-3.16]; P = .018). A low intraepithelial CD3(+)/FoxP3(+) cell ratio predicted reduced DFS (46.2% vs 66.7% survival at 5 years; HR, 2.17 [95% confidence interval, 1.11-4.23]; P = .0205). The prognostic impact of these markers was maintained when tumors were stratified by mismatch repair status. By multivariate analysis, a low CD3(+)/FoxP3(+) cell ratio (P= .0318) and low numbers of CD3(+) T cells (P = .0397) predicted shorter DFS times and were stronger prognostic variables than tumor stage or number of lymph node metastases.

conclusionsA low intraepithelial CD3(+)/FoxP3(+) cell ratio and reduced numbers of CD3(+) T cells were associated with shorter patient survival time, indicating the importance of an effector to Treg cell ratio in colon cancer prognosis.

Indexed as

AdenocarcinomaAgedAge FactorsCD3 ComplexCell DifferentiationColonic NeoplasmsDisease-Free SurvivalDNA Mismatch RepairEpithelial CellsFemaleFluorescent Antibody TechniqueForkhead Transcription FactorsHumansKaplan-Meier EstimateLymphocyte CountMaleCD3 ComplexForkhead Transcription FactorsFOXP3 protein, human

Identifiers

PMID19577568
PMCPMC2873775
OpenAlexW2042965540

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.