Abstract 448: The role of the Nanog transcription factor in tumor immune escape

Abstract

Abstract The emergence of cancer stem cells and escape from immune surveillance play major roles in the progression of many cancer types. We recently established a link between these two “hallmarks” of cancer by demonstrating that they are both driven by overexpression of Nanog, a pivotal transcription factor in the self-renewal of pluripotent stem cells. In particular, we found that tumor cells acquire Nanog expression in the course of immune selection, and that Nanog confers a stem-like and immune-resistant phenotype to these cells. However, the way in which Nanog causes this to occur remains largely unknown. We reasoned that Nanog-driven immune escape may be in part due to the effect of this transcription factor on the tumor microenvironment. Therefore, here we investigated the relationship between Nanog, immune selection, and the properties of the tumor microenvironment. We found that mice bearing tumor cells that underwent immune selection, compared to those bearing parental tumor cells (without immune selection), had markedly elevated levels of the cytokine IL-6 as well as of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment; both IL-6 and MDSCs have been well-documented to promote cancer immune escape. We further investigated the role of Nanog in setting up this microenvironment. To this end, we have devised an in vivo system that enables us to examine the relationship between Nanog expression in the tumor microenvironment and tumor growth in real-time. Taken together, we infer from these data that not only is Nanog induction a consequence of immune selection, but Nanog also plays an essential role in tumor immune escape. In fact, we found in multiple mouse and human tumor models that Nanog is necessary and sufficient for immune escape. Additionally, these results suggest that Nanog mediates immune escape by converting the tumor microenvironment into an immune-inhibitory site, through the induction of IL-6 and MDSCs. These studies authenticate the role of Nanog in cancer progression as a central instigator of tumor immune escape, and demonstrate its potential both as an important diagnostic/prognostic index and as a therapeutic target. Citation Format: Emily Robitschek, Chih-Ping Mao, Shiwen Peng, Chien-Fu Hung, TC Wu. The role of the Nanog transcription factor in tumor immune escape. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 448. doi:10.1158/1538-7445.AM2015-448