Evidence map›Paper›PMID 32861198›Full record

ArticleEBioMedicine2020

Molecular, clinicopathological, and immune correlates of LAG3 promoter DNA methylation in melanoma.

Anne Fröhlich, Judith Sirokay, Simon Fietz, Timo J Vogt, Jörn Dietrich, Romina Zarbl, Mike Florin, Pia Kuster, Gonzalo Saavedra, Susana Ramírez Valladolid and 12 more

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

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.8field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 66 citations in OpenAlex.

  1. Trial
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  10. Journal for immunotherapy of cancer · 2025
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  16. Review
  17. Molecular Pathways and Mechanisms of LAG3 in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  18. [Melanoma microenvironment-impact of modern therapies].Dermatologie (Heidelberg, Germany) · 2022
    Review
  19. Article
  20. Article
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

22 authors at 4 institutions in 2 countries.

Anne FröhlichDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Judith SirokayDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Simon FietzDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Timo J VogtDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Jörn DietrichDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Romina ZarblDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Mike FlorinDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Pia KusterDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Gonzalo SaavedraDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Susana Ramírez ValladolidDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Friederike HoffmannDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Lukas FlatzInstitute of Immunobiology, Kantonsspital St Gallen, St Gallen, Switzerland.; Department of Oncology and Haematology, Kantonsspital St Gallen, St Gallen, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Department of Dermatology and Allergology, Kantonsspital St Gallen, St Gallen, Switzerland.
Sandra S RingInstitute of Immunobiology, Kantonsspital St Gallen, St Gallen, Switzerland.; Microbiology and Immunology PhD Program, University of Zurich, Zurich, Switzerland.
Carsten GolletzInstitute of Pathology, University Hospital Bonn, Bonn, Germany.
Torsten PietschInstitute of Neuropathology, University Hospital Bonn, Bonn, Germany.
Sebastian StriethDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Peter BrossartDepartment of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany.
Gerrit H GielenInstitute of Neuropathology, University Hospital Bonn, Bonn, Germany.
Glen KristiansenInstitute of Pathology, University Hospital Bonn, Bonn, Germany.
Friedrich BootzDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Jennifer LandsbergDepartment of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Dimo DietrichDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. Electronic address: dimo.dietrich@gmail.com.
University Hospital Bonn · DEUniversity of Bonn · DEKantonsspital St. Gallen · CHUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe co-receptor lymphocyte-activation gene-3 (LAG3, LAG-3, CD223) is a potential target for immune checkpoint inhibition immunotherapies. However, little is known about the biological and clinical significance of LAG3 DNA methylation in melanoma and its microenvironment.

methodsWe evaluated LAG3 promoter and gene body methylation in a cohort of N = 470 melanoma patients obtained from The Cancer Genome Atlas (TCGA cohort), an independent cohort of N = 120 patients from the University Hospital Bonn, and in subsets of peripheral blood leukocytes, melanocytes, and melanoma cell lines. We validated the association of LAG3 methylation with mRNA expression in vitro in the melanoma cell line A375 treated with the hypomethylating agent 5-azacytidine and stimulated with interferon-γ. Finally, we investigated correlations between LAG3 methylation and progression-free survival in patients treated with immune checkpoint blockade (ICB cohort, N = 118).

findingsDepending on the analysed locus (promoter, gene body) we found region-dependent significant LAG3 methylation differences between monocytes, B cells, CD8

interpretationOur study points towards an epigenetic regulation of LAG3 via promoter methylation and suggests a prognostic and predictive significance of LAG3 methylation in melanoma. Our results give insight in the tumor cell-intrinsic transcriptional regulation of LAG3 in melanoma. In perspective, our results might pave the way for investigating LAG3 methylation as a predictive biomarker for response to anti-LAG3 immune checkpoint blockage.

fundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Indexed as

Biomarkers, TumorDNA MethylationPromoter Regions, GeneticAntigens, CDCell Line, TumorEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunotherapyKaplan-Meier EstimateLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingMelanomaMolecular Targeted TherapyNeoplasm GradingAntigens, CDBiomarkers, TumorLag3 protein, humanLymphocyte Activation Gene 3 ProteinDNA MethylationImmunotherapyLAG3MelanomaPredictive Biomarker

Identifiers

PMID32861198
PMCPMC7475111
OpenAlexW3081379550

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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.