Evidence map›Paper›PMID 34548385›Full record

ArticleJournal for immunotherapy of cancer2021

DNA methylation-based signature of CD8+ tumor-infiltrating lymphocytes enables evaluation of immune response and prognosis in colorectal cancer.

Qi Zou, Xiaolin Wang, Donglin Ren, Bang Hu, Guannan Tang, Yu Zhang, Meijin Huang, Rish K Pai, Daniel D Buchanan, Aung Ko Win and 4 more

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

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
4.6field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 66 citations in OpenAlex.

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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 5 institutions in 3 countries.

Qi Zou *Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Xiaolin Wang *Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Donglin Ren *Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Bang HuGuangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guannan TangGuangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Yu ZhangGuangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Meijin HuangGuangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Rish K PaiDepartment of laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
Daniel D BuchananColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
Aung Ko WinCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
Polly A NewcombDepartment of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA.
William M GradyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Huichuan Yu *Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China yuhch5@mail.sysu.edu.cn luoyx25@mail.sysu.edu.cn.ORCID 0000-0001-8357-1615
Yanxin Luo *Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China yuhch5@mail.sysu.edu.cn luoyx25@mail.sysu.edu.cn.ORCID 0000-0002-5200-3997
Sun Yat-sen University · CNUniversity of Washington · USMayo Clinic in Arizona · USThe Royal Melbourne Hospital · AUThe University of Melbourne · AU

Funding

Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
NCI NIH HHS U01 CA167551
6 · The paper itself

Abstract

backgroundTumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC).

methodsA CD8+ MeTIL signature score was constructed by using CD8+ T cell-specific differentially methylated positions (DMPs) that were identified from Illumina EPIC methylation arrays. Immune cells, colon epithelial cells, and two CRC cohorts (n=282 and 335) were used to develop a PCR-based assay for quantitative analysis of DNA methylation at single-base resolution (QASM) to determine CD8 + MeTIL signature score.

resultsThree CD8+ T cell-specific DMPs were identified to construct the CD8+ MeTIL signature score, which showed a dramatic discriminability between CD8+ T cells and other cells. The QASM assay we developed for CD8+ MeTIL markers could measure CD8+ TILs distributions in a fully quantitative, accurate, and simple manner. The CD8+ MeTIL score determined by QASM assay showed a strong association with histopathology-based CD8+ TIL counts and a gene expression-based immune marker. Furthermore, the low CD8+ MeTIL score (enriched CD8+ TILs) was associated with MSI-H tumors and predicted better survival in CRC cohorts.

conclusionsThis study developed a quantitative DNA methylation-based signature that was reliable to evaluate CD8+ TILs and prognosis in CRC. This approach has the potential to be a tool for investigations on CD8+ TILs and a biomarker for therapeutic approaches, including immunotherapy.

Indexed as

Biomarkers, TumorCD8-Positive T-LymphocytesColorectal NeoplasmsDNA MethylationHumansImmunityLymphocytes, Tumor-InfiltratingPrognosisBiomarkers, TumorbiomarkersCD8-positive T-lymphocytesgastrointestinal neoplasmsgenetic markerslymphocytestumortumor-infiltrating

Identifiers

PMID34548385
PMCPMC8458312
OpenAlexW3199786216

What OpenQuestion holds

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LicenceCC BY-NC
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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.