title: Protein-bound polysaccharide-K reduces the proportion of regulatory T cells in vitro and in vivo.
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.
authors.affiliation: Pharmaceuticals Division, Kureha Corporation, Tokyo, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Aoki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iijima
authors.forename: Mariko
authors.initials: M
authors.lastname: Kato
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Uchida
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Wada
authors.forename: Masatsune
authors.initials: M
authors.lastname: Murata
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Naritaka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoshimatsu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D005354:Fibrosarcoma / Q000188:drug therapy / Q000276:immunology; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood*; D019139:Tumor Escape / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C010770:polysaccharide-K; D007371:Interferon-gamma