Abstract 294: Sox2 remodels the tumor microenvironment via recruitment of Tregs

Abstract

Abstract Recent study showed that Sox2 gene, a key stem cell gene that maintains the pluripotency properties of embryonic stem cell (ESC) and cancer stem cell (CSC) plays an important role in the tumorigenesis and metastasis process of various types of tumor, however its regulatory effect on tumor microenvironment (TME) is still elusive. In this study, we established a BALB/c mice model xenografted with a mice breast cancer cell line-4T1 with down-regulation of Sox2 gene (4T1-shRNA-Sox2). We found that down-regulation of Sox2 inhibits the growth of tumors with a modulated immunomicroenvironment, which was reflected by the increased number of CD3+CD8+ T cells and expression level of Th1 cytokines, such as TFN-γ and decreased number of Foxp3+ Tregs and expression level of Th2 cytokines such as IL4, IL6 and IL10. In addition, the reduced expression level of vascular endothelial cell marker CD31 and lymphatic vessel marker Lyve-1 was also revealed in the 4T1-shRNA-Sox2 xenografted tumors. We further demonstrated that Sox2 modulates the TME by recruiting Tregs. By using real-time RT-PCR, we found the cytokines contributing to recruitment of Tregs, such as CCL1, CCL22, CCL28 and Cxcl12 reduced after Sox2 downregulation. In addition, the mRNA expression level of transcriptional factor NF-κB and its co-transcriptional factor RelA which controlled the expression of CCL1, CCL22 and CCL28 were also reduced. Consequently, our study revealed the functional interaction between tumor cells and the immunocytes in TME by demonstrated that Sox2 gene in tumor cells recruited Tregs to influence the tumor microenvironment thus promotes the growth of tumor. 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 294. doi:1538-7445.AM2012-294