Abstract 1566: Inhibition of TGF-β in tumor-draining lymph nodes can enhance the potency of dendritic cell-based vaccine immunotherapy

Abstract

Abstract Transforming growth factor-β (TGF-β), an immunosuppressive cytokine, produced in the tumor microenvironment will flow into tumor-draining lymph nodes where are primary priming sites for generation of anti-tumor immune responses, and play a critical role in suppressing anti-tumor immune responses. We focused on TGF-β-mediated immunosuppression in tumor draining lymph nodes, and examined whether local inhibition of TGF-β there could enhance the potency of dendritic cell (DC) -based vaccine immunotherapy in tumor-bearing mice. C57BL/6 mice bearing Lewis lung carcinoma (LLC1) subcutaneously were vaccinated with DCs loaded with LLC1-derived antigen. In order to inhibit TGF-β in tumor-draining lymph nodes, those mice were administered the plasmid DNA encoding the extracellular domain of TGF-β type II receptor fused to the human IgG heavy chain (TGFR DNA) near the established tumor intramuscularly. As results, the level of TGF-β in tumor-draining lymph nodes was decreased by administrations of TGFR DNA near the established tumor. In tumor-draining lymph nodes, the proliferative activity of FoxP3+ regulatory T cells was eliminated, whereas tumor antigen-specific CD8+ cells producing interferon-α were increased as compared with those in mice administered DC vaccine alone. In spleen, tumor antigen-specific cytotoxic as well as natural killer activity were augmented in mice administered DC vaccine with TGFR DNA. Subsequently, growth of the established tumor was suppressed effectively. In conclusion, inhibition of TGF-β-mediated immunosuppression in tumor-draining lymph nodes can significantly enhance the potency of DC vaccine. This animal model provides for a novel rationale with DC vaccine immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1566. doi:1538-7445.AM2012-1566