Secretion of the transforming growth factor-beta (TGF-beta) by tumor cells 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-beta signaling inhibitor, SB-431542, induces DC maturation in vitro when combined with protein-bound polysaccharide K (PSK). PSK has been used clinically as an anti-tumor agent in Japan. 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-beta 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 up regulation of CD83 expression of DCs and improved their abilities to produce IL-12. They also augmented the capacity of DCs to activate naïve T cells in allogeneic mixed lymphocyte reaction. These results suggested that PSK with TGF-beta receptor I kinase inhibitor should be able to induce antitumor immune response in immune-tolerant patients associated with TGF-beta activity.