Persistent activation of STAT3 plays a major role in
cancer progression and immune escape. Therefore, targeting STAT3 in
tumors is essential to enhance/reactivate antitumor immune response. In our previous studies, we demonstrated the efficacy of
stearic acid-modified
polyethylenimine (PEI-StA) in promoting
small interfering RNA (
siRNA) silencing of STAT3 in B16.F10
melanoma in vitro and in vivo. In the current study, we examine the immunologic impact of this intervention. Toward this goal, the infiltration and activation of lymphocytes and dendritic cells (DCs) in the
tumor mass were assessed using flow cytometry. Moreover, the levels of IFN-γ,
IL-12, and TNF-α in homogenized
tumor supernatants were determined. Moreover, mixed lymphocytes reaction using splenocytes of
tumor-bearing mice was used to assess DC functionality on
siRNA/lipopolyplexes intervention. Our results demonstrated up to an approximately fivefold induction in the infiltration of CD3(+) cells in
tumor mass on STAT3 knockdown with high levels of CD4(+), CD8(+), and NKT cells. Consistently, DC infiltration in
tumor milieu increased up to approximately fourfold. Those DCs were activated, in an otherwise suppressive microenvironment, as evidenced by a high expression of costimulatory molecules CD86 and CD40. ELISA analysis revealed a significant increase in IFN-γ,
IL-12, and TNF-α. Moreover, mixed lymphocytes reaction demonstrated alloreactivity of these DCs as assessed by high T-cell proliferation and
IL-2 production. Our results suggest a bystander immune response after local STAT3 silencing by
siRNA. This strategy could be beneficial as an adjuvant
therapy along with current
cancer vaccine formulations.