Tanaka Hiroaki, Yamazoe Sadaaki, Iwauchi Takehiko, Kubo Naoshi, Muguruma Kazuya, Yashiro Masakazu, Yamada Nobuya, Sawada Tetsuji, Ohira Masaichi, Hirakawa Kosei
Department of Surgical Oncology, Osaka City University Graduate School of Medicine.
Gan To Kagaku Ryoho. 2009 Nov;36(12):1969-71.
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.
