Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice

New strategies that stimulate cell-mediated immunity (CMI) against tumors and inhibit regulatory T cells are needed to improve the outcome of cancer immunotherapy. The aim of this study was to enhance the antitumor immunity of gp96 vaccine through naloxone administration. Therefore, we used BALB/c mouse model of fibrosarcoma tumor and analyzed the tumor size, splenocyte proliferation, spleen and tumor-infiltrated lymphocytes. Tumor and spleen CD4(+)CD25(+)Foxp3(+) regulatory T lymphocytes, cytotoxic activity of the splenocytes, IFN-gamma and IL-4 secretion were assessed to describe the anti-tumor immune response. Our findings showed that co-administration of gp96 and naloxone has resulted in a significant reduction in CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. The results indicated that on days 27 and 32 the tumors in the gp96 + Nal group grew significantly slower. Moreover, co-administration of gp96 and naloxone significantly increased the intra-tumor CD8(+) T cells and cytotoxic activity. In addition the results indicated a significant increase in the proliferation of splenocytes and IFN-gamma production. Our results demonstrate that naloxone is an effective immunoadjuvant in cancer immunotherapy. (C) 2009 Elsevier B.V. All rights reserved.