We next evaluated the gene silencing and antitumor effects of CpG-Stat3 siRNAs in vivo. Peritumoral injections of the CpG-Stat3 siRNA resulted in relatively effective gene silencing in DCs, macrophages and B cells in TDLNs, compared to control CpG-Luc siRNA, as measured by quantitative real-time PCR (Fig. 3c ). Stat3 inhibition in CD11c + DCs isolated from TDLNs was confirmed at protein level ( Fig. 3d) . Furthermore, quantitative real-time PCR and Western blotting indicated Stat3 silencing in the total TDLNs (Supplementary Fig.  10 ). We also used CpG-Luc siRNA conjugate to confirm that CpG-siRNA conjugates are able to reduce protein expression specifically within myeloid cells in vivo. Mice overexpressing firefly luciferase under control of the β-actin promoter 39 were challenged with tumor cells, followed by repeated peritumoral injections of CpG-Luc siRNA. Results from these experiments indicated effective inhibition of luciferase activity in CD11b + myeloid cells but not in CD4 + lymphocytes within TDLNs (Fig. 3e ).