Protein-bound polysaccharide-K reduces the proportion of regulatory T cells in vitro and in vivo

Aoki,Rieko; Iijima,Hiroko; Kato,Mariko; Uchida,Motoyuki; Wada,Tsutomu; Murata,Masatsune; Ogawa,Kenji; Naritaka,Yoshihiko; Yoshimatsu,Kazuhiko

doi:10.3892/or.2013.2834

Protein-bound polysaccharide-K reduces the proportion of regulatory T cells in vitro and in vivo

Authors:
- Rieko Aoki
- Hiroko Iijima
- Mariko Kato
- Motoyuki Uchida
- Tsutomu Wada
- Masatsune Murata
- Kenji Ogawa
- Yoshihiko Naritaka
- Kazuhiko Yoshimatsu
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Affiliations: Pharmaceuticals Division, Kureha Corporation, Tokyo, Japan, Department of Nutrition and Food Science, Ochanomizu University, Tokyo, Japan, Department of Surgery, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan
Published online on: November 4, 2013 https://doi.org/10.3892/or.2013.2834
Pages: 50-56

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Abstract

Regulatory T cells (Tregs) play an important role in maintaining immunological tolerance. However, this mechanism is one of the major obstacles to overcome when attempting to improve antitumor immunity. Protein-bound polysaccharide‑K (PSK) has been used clinically as an antitumor drug, and one of its antitumor mechanisms involves improvement of the tumor-induced immunosuppressive state. Therefore, we investigated whether PSK affects Tregs in vitro and in vivo. In the in vitro study, CD4+CD25- cells were separated from normal mouse spleen and cultured with or without PSK in the presence of TGF-β. Although TGF-β induced CD4+CD25+Foxp3+ Tregs, PSK reduced the proportion of TGF-β-induced Tregs. In the in vivo study, BALB/c mice were injected subcutaneously with methylcholanthrene-induced fibrosarcoma (Meth A) cells on day 0, and were administered PSK (50 mg/kg) intraperitoneally from day 1, three times per week. After 4 weeks, the tumor volume, the proportion of Tregs and the CD8+/Treg ratio in the spleen, plasma TGF-β concentration, and IFN-γ production by spleen cells were measured. PSK significantly reduced tumor growth, the proportion of Tregs in the spleen and the plasma TGF-β concentration, and significantly increased the CD8+/Treg ratio in the spleen and IFN-γ production by spleen cells. The reduction of the TGF-β concentration in blood by PSK appears to decrease the proportion of Tregs in lymphoid organs and to augment antitumor immunity.

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