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Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Epigenetic quantification of tumor-infiltrating T-lymphocytes
Jalid Sehouli1, Christoph Loddenkemper, Tatjana Cornu
1Klinik für Frauenheilkunde, Charité-Universitätsmedizin, Campus Virchow, Berlin, Germany.
Epigenetics
|October 22, 2010
Summary
Epigenetic immunophenotyping quantifies T-lymphocytes and regulatory T-cells (Treg) in tumors. This method reveals altered T-cell composition in solid tumors, impacting immune evasion and patient prognosis.
Area of Science:
- Immunology
- Oncology
- Epigenetics
Background:
- The tumor microenvironment's immune cell composition is crucial for tumor progression.
- Regulatory T-cells (Treg) suppress anti-tumor immunity, but their quantification in solid tumors is challenging.
- Existing methods for cell quantification in tissues have limitations.
Purpose of the Study:
- To develop and validate an epigenetic immunophenotyping method for quantifying T-lymphocytes and Treg in solid tissues.
- To analyze the frequency and ratio of Treg to overall T-lymphocytes (oTL) in various cancer types.
- To investigate the correlation between epigenetic T-cell quantification and patient outcomes.
Main Methods:
- Expanded epigenetic immunophenotyping to quantify overall T-lymphocytes (oTL) using epigenetic marks.
- Applied the method to analyze 616 human tissue samples (ovarian, colorectal, bronchial) from healthy and tumorous individuals.
- Correlated epigenetic T-cell frequencies with clinical data and patient outcomes.
Main Results:
- The developed epigenetic method provides precise cell quantification comparable to FACS, applicable to blood and solid tissues.
- A significant shift in the median Treg-to-oTL ratio was observed, increasing from 3-8% in healthy tissues to 18-25% in tumor tissues across all analyzed cancer types.
- Epigenetically determined oTL frequencies correlated with prognosis in colorectal and ovarian cancers.
Conclusions:
- Epigenetic immunophenotyping is a robust tool for quantitative assessment of immune cell composition in tumor microenvironments.
- Solid tumors exhibit a disturbed immune cell composition, characterized by an increased Treg-to-oTL ratio, suggesting a mechanism of immune evasion.
- Epigenetic quantification of T-lymphocytes offers an independent clinical parameter for predicting patient outcomes in cancer.
