Abstract LB-348: Negative roles of C/EBPα in MDSC-mediated tumor angiogenesis and immune suppression

Abstract

Abstract Myeloid-derived suppressor cells (MDSCs) are highly increased in peripheral blood of cancer patients, as well as tumor bearing animal models. These cells have long been known to suppress the host immune response to cancer. In the present study, we found that CCAAT/enhancer binding protein alpha (C/EBPα) expression was significantly reduced in MDSCs from tumor-bearing mice compared to non-tumor-bearing hosts. Tumor-conditioned medium down-regulated C/EBPα expression, suggesting tumor secreted factors inhibiting the gene expression. Consistent with the function of C/EBPα in regulating the balance between proliferation and growth arrest in hematopoietic progenitors, the specific deletion of C/EBPα on myeloid lineage resulted in distinctly enhanced the proliferation and expansion of MDSCs, as well as an increase of myeloid progenitors and a decrease of other mature cells. In addition, the deletion of C/EBPα in MDSCs enhanced the pro-angiogenic, immune suppressive and pro-tumorigenic behavior of these cells by upregulating the production of iNOS and arginase, as well as MMP-9 and VEGF. Accordingly, tumors growing in C/EBPα conditional null mice displayed greater MDSC infiltration, increased vascularization and accelerated tumor growth. Taken together, this study reveals dual negative roles of C/EBPα in the expansion as well as pro-angiogenic and immune suppressive functions in MDSCs. Citation Format: Peng Qu, Yongfen Min, Li Yang, Charles Lin. Negative roles of C/EBPα in MDSC-mediated tumor angiogenesis and immune suppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-348.