Abstract 5404: Up-regulation of proliferative and migratory genes in regulatory T cells from patients with metastatic castration-resistant prostate cancer

Immune suppression by regulatory T cells (Tregs) is associated with tumor evasion. An increase in the frequency and suppressive function of Tregs has been shown in a variety of solid tumors. The purpose of this study was to determine if the enhanced number and activity of these cells in prostate cancer patients could be due to tumor-induced changes in gene expression. CD4+CD25hiCD127lo Tregs were isolated from the peripheral blood of healthy donors and metastatic castration-resistant prostate cancer (mCRPC) patients. These samples were selected based on similar suppressive activity in a functional assay. A genome-wide expression array of 38, 500 genes was then performed to detect any effects in expression potentially induced by tumor. We found 384 genes had a three-fold or greater difference in expression between the groups. Differentially expressed genes were involved in cell cycle processes, cellular growth and proliferation, immune response, hematological system development and function, as well as the IL-2 and TGF-β pathways. Genes most up-regulated in the Tregs of mCRPC patients included C-FOS, C-JUN, DUSP1 and RGS1, which are crucial for regulation of T cell proliferation, activation and migration. We also observed increased expression of c-Jun protein in patient Tregs by flow cytometry. Patients had a significantly higher percentage of Tregs in their CD4+ population than the healthy donors, but interestingly, there was no difference in FoxP3 expression. These results indicate that tumor-derived factors may contribute to Treg mediated immune suppression by up-regulating genes that increase their proliferative and migratory capacities, allowing them to better home to the tumor and inhibit the host response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5404. doi:1538-7445.AM2012-5404