Abstract POSTER-BIOL-1332: Molecular, cellular and clinical interaction between MDSC and ovarian cancer stemness

Abstract

Abstract Myeloid derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are important cellular components in the cancer microenvironment, and may affect cancer phenotype and patient outcome. The nature of MDSCs and their interaction with CSCs in ovarian carcinoma are unclear. We examined the interaction between MDSCs and CSCs in patients with ovarian carcinoma. We demonstrate that MDSCs inhibit T cell activation, enhance CSC gene expression, sphere formation and cancer metastasis. MDSCs trigger microRNA101 expression in cancer cells; microRNA101 subsequently represses the co-repressor gene C-terminal binding protein-2 (CtBP2), and CtBP2 directly targets stem cell core genes resulting in increased cancer cell stemness, and increasing metastatic and tumorigenic potential. Increased MDSC density and tumor microRNA101 levels, and decreased tumor CtBP2 expression independently predict poor survival. Collectively, the work identifies a novel immune associated cellular, molecular and clinical network involving MDSCs/microRNA101/CtBP2/stem cell core genes, which extrinsically controls cancer stemness and impacts patient outcome. Citation Format: Ilona Kryczek, Tracy X. Cui, Lili Zhao, Linda Vatan, Wojciech Szeliga, Rebecca Liu, Weiping Zou. Molecular, cellular and clinical interaction between MDSC and ovarian cancer stemness [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1332.