Fig 1: Midkine inhibition prevents immunosuppressive MDSCs infiltrating into HCC tumors.Hepa 1-6 cells transduced with Sh-MDK-1, Sh-MDK-2 or Sh-NC lentivirus were orthotopically implanted into the liver of C57BL/6 mice, then treated with sorafenib (Sor) or vehicle control (Veh) for three weeks. A protein expression of midkine in midkine-depleted orthotopic Hepa 1-6 tumors was validated by western blot. B, C Ly6CintLy6G+ PMN-MDSCs and Ly6ChighLy6G- M-MDSCs in intratumoral CD11b+Gr-1+ subset of midkine-depleted orthotopic Hepa 1-6 tumors were evaluated by flow cytometry. D–F Arg1+ cells in infiltrating CD11b+Gr-1+ subset (D–E) and MDSCs subset (F) of midkine-depleted orthotopic Hepa 1-6 tumors were evaluated by flow cytometry. G, H infiltrating PMN-MDSCs and M-MDSCs of midkine-depleted orthotopic Hepa 1-6 tumors were used for T-cell suppression assay. Ki67+ (G) and Granzyme B+ (H) cytotoxic T cells were evaluated by flow cytometry. All assays were done with at least three repeats. Data were shown as mean ± s.d., *P < 0.05.
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