Evidence map›Paper›PMID 39440906›Full record

ArticleCancer science2025

FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor.

Suguru Maruyama, Yu Imamura, Tasuku Toihata, Ikumi Haraguchi, Manabu Takamatsu, Makiko Yamashita, Yuichiro Nakashima, Eiji Oki, Kenichi Taguchi, Manabu Yamamoto and 8 more

Abstract read
In one paragraph

Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
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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

18 authors.

Suguru MaruyamaDepartment of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Yu ImamuraDepartment of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID https://orcid.org/0000-0002-0036-0124
Tasuku ToihataDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Ikumi HaraguchiCancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Manabu TakamatsuDepartment of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID https://orcid.org/0000-0001-9601-5802
Makiko YamashitaAdvanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Yuichiro NakashimaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Eiji OkiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.ORCID https://orcid.org/0000-0002-9763-9366
Kenichi TaguchiDepartment of Pathology, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan.
Manabu YamamotoDepartment of Gastroenterological Surgery, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan.
Shinji MineDepartment of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, Tokyo, Japan.
Akihiko OkamuraDepartment of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Jun KanamoriDepartment of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Souya NunobeDepartment of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Takeshi SanoDepartment of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Shigehisa KitanoAdvanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID https://orcid.org/0000-0002-4041-8298
Tetsuo NodaCancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Masayuki WatanabeDepartment of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Funding

Foundation for Promotion of Cancer ResearchJapan Research Foundation for Clinical PharmacologyJapan Society for the Promotion of Science JP19K09161Japan Society for the Promotion of Science JP19K09231Japan Society for the Promotion of Science JP20K09046Japan Society for the Promotion of Science JP24K11921Uehara Memorial Foundation
6 · The paper itself

Abstract

The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.

Indexed as

AdenocarcinomaCD8-Positive T-LymphocytesCore Binding Factor Alpha 3 SubunitEsophageal NeoplasmsEsophagogastric JunctionForkhead Transcription FactorsStomach NeoplasmsTumor MicroenvironmentAdultAgedAged, 80 and overDNA MethylationFemaleHumansLymphocytes, Tumor-InfiltratingMaleCore Binding Factor Alpha 3 SubunitForkhead Transcription FactorsFOXP3 protein, humanRunx3 protein, humanchemokinediffuse histologyeffector T cellesophagogastric junction adenocarcinomaregulatory T cell

Identifiers

PMID39440906
PMCPMC11711055

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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.