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

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-. Although TGF- induced CD4(+)CD25(+)Foxp3(+) Tregs, PSK reduced the proportion of TGF--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- concentration, and IFN- production by spleen cells were measured. PSK significantly reduced tumor growth, the proportion of Tregs in the spleen and the plasma TGF- concentration, and significantly increased the CD8(+)/Treg ratio in the spleen and IFN- production by spleen cells. The reduction of the TGF- concentration in blood by PSK appears to decrease the proportion of Tregs in lymphoid organs and to augment antitumor immunity.