[Impacts of PSK and TbetaR inhibitor on immune response in immunosuppressive status associated with cancer].
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.
Tanaka
Hiroaki
H
Department of Surgical Oncology, Osaka City University Graduate School of Medicine.
Yamazoe
Sadaaki
S
Iwauchi
Takehiko
T
Kubo
Naoshi
N
Muguruma
Kazuya
K
Yashiro
Masakazu
M
Yamada
Nobuya
N
Sawada
Tetsuji
T
Ohira
Masaichi
M
Hirakawa
Kosei
K
D001549:Benzamides / Q000008:administration & dosage; D003713:Dendritic Cells / Q000187:drug effects; D004149:Dioxoles / Q000008:administration & dosage; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007155:Immunologic Factors / Q000008:administration & dosage*; D066298:In Vitro Techniques; D011509:Proteoglycans / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D007155:Immunologic Factors; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C010770:polysaccharide-K