In the present study, we showed that a local injection of relatively low-dose (0.5–2.5 mg/kg body weight) CpG-Stat3 siRNA, in which CpG represents roughly a quarter of the conjugate, is effective in increasing both CTLA4 and PD-1 antibody-mediated antitumor immune responses, including recruitment and activation of tumor CD8+ T cells, reduction of tumor-infiltrating CD4+ Tregs, and improved antitumor effects. Here, CD4 is linked to neoplasm.