Abstract 5603: Impact of combination of PSK with TGF-beta inhibitor on anti-tumor immunity

Abstract

Abstract The transforming growth factor-β (TGF-β) has a role in tumor progression and metastasis. Secretion of TGF-β by tumor cells also suppresses an antitumor immune response in which dendritic cells (DCs) play an important role to activate cytotoxic T lymphocytes (CTLs). Here we report that small molecule TGF-β signaling inhibitor, SB-431542 (SB), induce DC maturation in vitro when combined with Protein-bound polysaccharide K (PSK). PSK has been used clinically as an anti-tumor agent in Japan. It has been reported that PSK have potential to induce anti-tumor immune response. In this study, we examined the impact of PSK and SB-431542 on maturation of DCs under immunological tolerant status. At first, we added SB and PSK to cultures of human DCs generated from peripheral monocytes in the presence of TGF-β and examined expression of CD83, production of Interleukin-12 (IL-12) and capacity of DCs to induce T cell proliferation. SB-431542 with PSK induced upregulation of CD83 of human DCs and improved their abilities to produce interleukin 12. They also augmented capacity of human DCs to activate naïve T cells in allogeneic mixed lymphocyte reaction. These results suggested that TGF-β receptor I kinase inhibitor such as SB-431542 should be able to induce antitumor immune response in immuno-tolerant patients associated with TGF-β activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5603.