The anti-tumor effect of resveratrol alone or in combination with immunotherapy in a neuroblastoma model.

We investigated the anti-tumor effect of peritumoral resveratrol in combination with immunotherapy in vivo in neuroblastoma-bearing mice. Subcutaneous NXS2 tumors were induced in A/J mice. On day 10, some mice received 15 mcg of intravenous immunocytokine for 5 days, mice received 20 mg of peritumoral resveratrol twice a week (starting on day 12) for a total of 5 injections, and a separate group received a combination of both regimens. Tumor progression and survival were assessed every 3-4 days. Blood and primary tumor tissue samples were collected on day 20 for Complete Blood Count and CD45 immunohistochemistry and histology, respectively. The primary tumor regressed in all mice receiving peritumoral resveratrol. Most of these mice receiving peritumoral resveratrol alone developed metastatic tumors and recurrence of the primary tumor after cessation of therapy. When resveratrol and immunocytokine regimens were combined, 61% of the mice receiving this combination therapy resolved their primary tumors and survived without developing metastatic tumors, compared to 15 and 13% receiving resveratrol or immunocytokine alone, respectively. None of the therapeutic regimes prevented lymphocyte infiltration or affected the complete blood count. Greater necrosis was observed microscopically in tumors from mice receiving the combination therapy. These results demonstrate that the combination therapy of peritumoral resveratrol plus intravenous immunocytokine provides better anti-tumor effects in this model than either therapy alone.

Anti-tumor and immunomodulatory activity of resveratrol in vitro and its potential for combining with cancer immunotherapy.

We evaluated the anti-tumor effect of Resveratrol (RV) on M21 and NXS2 tumor cell lines and its immunosuppressive activity on human and murine immune cells to determine the potential for combining RV and immunotherapy. In vitro, concentrations of RV≥25 mcM, inhibited cell proliferation, blocked DNA synthesis and induced G1 phase arrest in tumor and immune cells. RV at 12-50 mcM inhibited antibody dependent cell mediated cytotoxicity (ADCC) of tumor cells facilitated by the hu14.18-IL2 immunocytokine (IC). The in vivo anti-tumor and immunomodulating activity of RV given systemically were assessed in mice. Results showed that this RV regimen inhibited the growth of NXS2 tumors in vivo but did not appear to interfere with blood cell count, splenocyte or macrophage function. Thus, RV may be a candidate for combining with immunotherapy.