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Epigenetics
Article . 2011 . Peer-reviewed
Data sources: Crossref
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Epigenetics
Article
Data sources: UnpayWall
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Epigenetics
Article . 2011
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Epigenetic quantification of tumor-infiltrating T-lymphocytes

Authors: Jalid, Sehouli; Christoph, Loddenkemper; Tatjana, Cornu; Tim, Schwachula; Ulrich, Hoffmüller; Andreas, Grützkau; Philipp, Lohneis; +7 Authors

Epigenetic quantification of tumor-infiltrating T-lymphocytes

Abstract

The immune system plays a pivotal role in tumor establishment. However, the role of T-lymphocytes within the tumor microenvironment as major cellular component of the adaptive effector immune response and their counterpart, regulatory T-cells (Treg), responsible for suppressive immune modulation, is not completely understood. This is partly due to the lack of reliable technical solutions for specific cell quantification in solid tissues. Previous reports indicated that epigenetic marks of immune cells, such as the Treg specifically demethylated region (TSDR) within the FOXP3 gene, may be exploited as robust analytical tool for Treg-quantification. Here, we expand the concept of epigenetic immunophenotyping to overall T-lymphocytes (oTL). This tool allows cell quantification with at least equivalent precision to FACS and is adoptable for analysis of blood and solid tissues. Based on this method, we analyse the frequency of Treg, oTL and their ratio in independent cohorts of healthy and tumorous ovarian, colorectal and bronchial tissues with 616 partly donor-matched samples. We find a shift of the median ratio of Treg-to-oTL from 3-8% in healthy tissue to 18-25% in all tumor entities. Epigenetically determined oTL frequencies correlate with the outcome of colorectal and ovarian cancers. Together, our data show that the composition of immune cells in tumor microenvironments can be quantitatively assessed by epigenetic measurements. This composition is disturbed in solid tumors, indicating a fundamental mechanism of tumor immune evasion. Epigenetic quantification of T-lymphocytes serves as independent clinical parameter for outcome prognosis.

Keywords

Epigenomics, Male, Ovarian Neoplasms, CD3 Complex, Forkhead Transcription Factors, DNA Methylation, Prognosis, Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Lymphocytes, Tumor-Infiltrating, Neoplasms, Tumor Microenvironment, Humans, Female, Lymphocyte Count, Colorectal Neoplasms

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    80
    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
80
Top 10%
Top 10%
Top 10%
gold