Back to Search Start Over

Regulatory T-Cells and Associated Pathways in Metastatic Renal Cell Carcinoma (mRCC) Patients Undergoing DC-Vaccination and Cytokine-Therapy.

Authors :
Schwarzer, Adrian
Wolf, Benita
Fisher, Jan L.
Schwaab, Thomas
Olek, Sven
Baron, Udo
Tomlinson, Craig R.
Seigne, John D.
Crosby, Nancy A.
Gui, Jiang
Hampton, Thomas H.
Fadul, Camilo E.
Heaney, John A.
Ernstoff, Marc S.
Source :
PLoS ONE; Oct2012, Vol. 7 Issue 10, Special section p1-12, 12p
Publication Year :
2012

Abstract

Purpose: To evaluate CD4<superscript>+</superscript>CD25<superscript>+</superscript>FOXP3<superscript>+</superscript> T regulatory cells (T<subscript>REG</subscript>) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating T<subscript>REG</subscript> combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis. Design: Eighteen patients with mRCC and twelve volunteers (controls) were available for analysis. T<subscript>REG</subscript> phenotype was examined using flow cytometry (FCM). T<subscript>REG</subscript> were also quantified by analyzing the epigenetic status of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of the PBL was hybridized to Affymetrix GeneChip Human Gene 1.0 ST Arrays and the gene signatures were explored using pathway analysis. Results: We observed higher numbers of T<subscript>REG</subscript> in pre-treatment PBL of mRCC patients compared to controls. A significant increase in T<subscript>REG</subscript> was detected in all mRCC patients after the two cycles of immunotherapy. The expansion of T<subscript>REG</subscript> was significantly higher in non-responders than in responding patients. Methylation specific PCR confirmed the FCM data and circumvented the variability and subjectivity of the FCM method. Gene Set Enrichment Analysis (GSEA) of the microarray data showed significant enrichment of FOXP3 target genes, CTLA-4 and TGF-ß associated pathways in the patient cohort. Conclusion: Immune monitoring of the peripheral blood and tumor tissue is important for a wide range of diseases and treatment strategies. Adoption of methodology for quantifying T<subscript>REG</subscript> with the least variability and subjectivity will enhance the ability to compare and interpret findings across studies. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
7
Issue :
10
Database :
Complementary Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
83522872
Full Text :
https://doi.org/10.1371/journal.pone.0046600