Lnc-chop Promotes Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor and Inflammatory Environments

Abstract

Myeloid-derived suppressor cells (MDSCs) are major regulators of immune responses in cancer. Both C/EBP homologous protein (CHOP) and C/EBPβ play a critical role in regulating immunosuppressive function of MDSCs. In this study, we identified a novel long noncoding RNA termed as lnc-chop in MDSCs, which may interact with CHOP and the C/EBPβ isoform liver-enriched inhibitory protein. The binding of lnc-chop with both CHOP and the C/EBPβ isoform liver-enriched inhibitory protein promoted the activation of C/EBPβ and upregulated the expression of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2, which are related to the immunosuppressive function of MDSCs in inflammatory and tumor environments. Additionally, lnc-chop also promoted the enrichment of H3K4me3 on the promoter region of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2. These findings suggest an important role of lnc-chop in controlling immunosuppressive function of MDSCs in the tumor environment.