Lnc-C/EBPβ negatively regulates immune-suppressive function of MDSCs in vivo. Lnc-C/EBPβ negatively regulates immune-suppressive function of MDSCs in vivo.

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Lnc-C/EBPβ negatively regulates immune-suppressive function of MDSCs in vivo. Lnc-C/EBPβ negatively regulates immune-suppressive function of MDSCs in vivo. A, Schematic of the experiments. B–D, Mouse melanoma growth curve (B), tumor size (C), and tumor weights (D) in mice infused with lnc-C/EBPβ knockdown (kdLnc) and exogenous lnc-C/EBPβ (oeLnc)-treated MDSCs (6 mice/group). E–G, Mouse Lewis lung cancer growth curve (E), tumor size (F), and tumor weights (G) in mice infused with lnc-C/EBPβ knockdown and exogenous lnc-C/EBPβ-treated MDSCs (n = 6). H and I, Flow cytometry of CD4+ and CD8+ T-cell populations in the tumor tissues of mice bearing OVA-B16 tumor after infusing gain-of-function and loss-of-function MDSCs. The proportion of CD4+ and CD8+ T cells was compared (n = 6; I). J and K, IFNγ in the supernatants of CD4+ and CD8+ T cells isolated from tumor tissues of mice bearing OVA-B16 tumor after infusing gain-of-function and loss-of-function MDSCs (n = 6). L and M, Flow cytometry of CD45.1+ Ly6G+Ly6C+ MDSC subsets in tumor tissues of mice bearing OVA-B16 tumors after infusing gain-of-function and loss-of-function MDSCs. Percentage changes of CD45.1+ Ly6G+Ly6C+ (Ly6G+) and CD45.1+ Ly6G−Ly6C+ (Ly6G−) MDSC subsets in the tumor site were compared (M, 6 mice/group). N, Confocal microscopy of CD45.1+ cells in the tumor site and spleen. Green: CD45.1; Blue: nuclei. NC: isotypic antibody. Scale bar: 50 μmol/L. kdLnc: lentivirus/lnc-C/EBPβ shRNA; oeLnc: lentivirus/lnc-C/EBPβ; kdNC and oeNC: control lentiviruses. Two-way ANOVA was used in B and E. Two-tailed, paired t test was used in D, G, I, J, K, and M. *, P < 0.05; **, P < 0.01; ***, P < 0.001. NS, not significant. Data are representative of two independent experiments. Yunhuan Gao et al. Cancer Immunol Res 2018;6:1352-1363 ©2018 by American Association for Cancer Research