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-naive 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 antiapoptotic 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. Copyright (C) 2009 S. Karger AG, Basel