Lnc-C/EBPβ negatively regulates the suppressive function of myeloid-derived suppressor cells

Abstract

Myeloid-derived suppressor cells (MDSC) are regulators of immune responses in cancer. The differentiation and function of these MDSCs may be regulated through multiple factors, such as microRNAs. However, the effect of long noncoding RNAs (lncRNA) on the differentiation and function of MDSCs is poorly understood. We identified a long noncoding RNA (lncRNA) named lnc-C/EBPβ in MDSCs, which may control suppressive functions of MDSCs. Lnc-C/EBPβ could be induced in in vitro and in vivo tumor and inflammatory environments. It regulated a set of target transcripts, such as Arg-1, NOS2, NOX2, and COX2, to control immune-suppressive function and differentiation of MDSCs. This lncRNA was also able to bind to the C/EBPβ isoform LIP to inhibit the activation of C/EBPβ. We also found that the conserved homologue lnc-C/EBPβ has a similar function to murine lnc-C/EBPβ. These findings suggest a negative feedback role for lnc-C/EBPβ in controlling the immunosuppressive functions of MDSC in the tumor environment.