MDSC-derived IL-6 enhances tumor progression through the inhibition of tumor-specific TH1 development and of their helper activity for CD8+ T cells. MDSC-derived.

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MDSC-derived IL-6 enhances tumor progression through the inhibition of tumor-specific TH1 development and of their helper activity for CD8+ T cells. MDSC-derived IL-6 enhances tumor progression through the inhibition of tumor-specific TH1 development and of their helper activity for CD8+ T cells. A–C, OT-II cells, IL-6+/+, or IL-6−/− MDSC (3 × 106) and recombinant sIL-6R were injected into naïve mice followed by transfer of dendritic cell (DC). Seven days after immunization, the number of donor OT-II cells in pooled lymph nodes and spleens (C) and the frequency of IFN-γ+ cells in donor OT-II cells restimulated with peptide-pulsed dendritic cell (D) were determined. E, MCA205-OVA were inoculated 1 week after immunization as in B. Six days later, draining lymph nodes were analyzed for OVA peptide (SIINFEKL)/H-2Kb-tetramer+CD8+CD44hi cells. Representative plots (left) and the number of OVA-specific CD8+ T cells (right) are shown. F and G, 1 week after immunization as in B, MCA205-OVA (F) or MO4 (G) were injected subcutaneously or intravenously, respectively. In the pulmonary metastatic model using luciferase-transfected MO4, luminescence images at day 30 after inoculation (left) and photon-counts per mouse (right) are shown. Data for tumor growth shown here are mean ± SEM with n = 8–10 mice per group. *, P < 0.05; **, P < 0.01; ***, P < 0.005. Representative of 2 experiments. WT, wild-type; KO, knockout; NS, no significant. Hirotake Tsukamoto et al. Cancer Immunol Res 2013;1:64-76 ©2013 by American Association for Cancer Research