Frequency and gene expression profile of regulatory T cells in renal cell carcinoma.
CD4(+)CD25(high) regulatory T cells (T(reg)) have the potent ability to suppress host immune responses, thus preventing autoimmune diseases. However, increased T(reg) frequencies have also been found in cancer patients implicating their involvement in tumor escape from immunological control. We investigated the frequency, functional effects and gene expression pattern of T(reg) in patients with renal cell carcinoma (RCC). Therefore, T(reg) were isolated from the peripheral blood of 11 treatment-naïve RCC patients and 11 healthy donors applying a magnetic cell separation system. Frequency, purity after isolation and function were evaluated using FACS and suppression assays, respectively. Gene expression patterns were compared applying a self-developed customized oligonucleotide microarray and by quantitative RT-PCR. T(reg) frequencies were significantly increased in RCC patients; suppression assays proved that the isolated CD4(+)CD25(high) cells had the functional characteristics of T(reg) cells. Comparing gene expression profiles between T(reg )of RCC patients and healthy controls revealed significant differences in the expression levels of 49 genes. Gene ontology identified an association of significantly up-/downregulated genes to six functional classes, particularly genes involved in apoptosis control such as LGALS1, LGALS3, BAX, IL7R and TNFRSF25. In RCC patients, frequencies of functionally active T(reg) cells were elevated; the T(reg) gene expression pattern differed significantly between patients and controls. As several anti-apoptotic genes were upregulated and pro-apoptotic genes were downregulated in RCC patients, we conclude that T(reg) cells derived from RCC patients might be less responsive to apoptotic stimuli, possibly promoting their accumulation in tumor patients.
Jeron
Andreas
A
Department of Cell Biology, Immune Regulation Group, Helmholtz Center for Infection Research, Braunschweig, Germany.
Pfoertner
Susanne
S
Bruder
Dunja
D
Geffers
Robert
R
Hammerer
Peter
P
Hofmann
Rainer
R
Buer
Jan
J
Schrader
Andres Jan
AJ
D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors