Evidence map›Paper›PMID 35410311›Full record

ArticleClinical epigenetics2022

DNA methylation regulates TIGIT expression within the melanoma microenvironment, is prognostic for overall survival, and predicts progression-free survival in patients treated with anti-PD-1 immunotherapy.

Dennis Niebel, Anne Fröhlich, Romina Zarbl, Simon Fietz, Luka de Vos, Timo J Vogt, Jörn Dietrich, Judith Sirokay, Pia Kuster, Gonzalo Saavedra and 5 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

23 citing papers in PubMed, 29 citations in OpenAlex.

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  10. Journal for immunotherapy of cancer · 2025
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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

15 authors at 1 institution in 1 country.

Dennis Niebel *Department of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Anne Fröhlich *Department of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Romina ZarblDepartment of Otorhinolaryngology, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Simon FietzDepartment of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Luka de VosDepartment of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Timo J VogtDepartment of Otorhinolaryngology, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Jörn DietrichDepartment of Otorhinolaryngology, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Judith SirokayDepartment of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Pia KusterDepartment of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Gonzalo SaavedraDepartment of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Susana Ramírez ValladolidDepartment of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Friederike HoffmannDepartment of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Sebastian StriethDepartment of Otorhinolaryngology, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Jennifer Landsberg *Department of Dermatology and Allergy, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany.
Dimo Dietrich *Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Venusberg-Campus 1, 53127, Bonn, Germany. Dimo.Dietrich@gmail.com.ORCID 0000-0001-9794-7927
University of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTIGIT is an immune checkpoint under investigation as therapeutic target. Understanding the regulation of TIGIT on an epigenetic level might support the development of companion biomarkers.

methodsWe correlated TIGIT DNA methylation of single CpG sites with gene expression, signatures of immune infiltrates and interferon-γ, and survival in melanoma. We further analyzed methylation levels in immune cell subsets, melanocyte and melanoma cell lines. TIGIT expression patterns within components of the melanoma microenvironment were analyzed by single cell sequencing. We used quantitative methylation-specific PCR, flow cytometry, and immunohistochemistry for correlations between expression and methylation and to assess the effect of pharmacological demethylation of melanoma cells treated with 5-aza-2-deoxycytidine (decitabine). Finally, we investigated the association of patients' survival with TIGIT mRNA and methylation.

resultsDepending on the sequence context of the analyzed CpG site, we found a cell type-specific TIGIT gene locus methylation pattern and significant correlations of TIGIT methylation with mRNA expression, an interferon γ signature, and distinct immune cell infiltrates, including TIGIT

conclusionsOur data demonstrate an epigenetic regulation of TIGIT expression via DNA methylation within the melanoma microenvironment. TIGIT DNA methylation and expression may serve as predictive biomarkers in the context of immunotherapies in melanoma.

Indexed as

DNA MethylationMelanomaEpigenesis, GeneticHumansImmunotherapyPrognosisProgression-Free SurvivalReceptors, ImmunologicRNA, MessengerTumor MicroenvironmentReceptors, ImmunologicRNA, MessengerTIGIT protein, humanBiomarkerDNA methylationImmunotherapyMelanomaT Cell Ig and ITIM Domain (TIGIT)

Identifiers

PMID35410311
PMCPMC9004005
OpenAlexW4223526159

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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.