Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer

  • 37 Accesses

  • 19 Citations


The present study was designed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration <14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (≧14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group.

These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL. Thus, increased numbers of cytotoxic effector cells appear to be activated in the PBL while helper T cells predominate in the RNL.

This is a preview of subscription content, log in to check access.



antibody dependent cell-mediated cytotoxicity




Hanks' balanced salt solution




natural killer


peripheral blood lymphocytes




poke weed mitogen


recombinant IL-2


regional node lymphocytes


  1. 1.

    Akiyama J, Kawamura T, Gotohda E, Yamada Y, Hosokawa M, Kodama T, Kobayashi H. Immunochemotherapy of transplanted KMT-17 tumor in WKA rats by combination of cyclophosphamide and immunostimulatory protein-bound polysaccharide isolated from basidiomycetes. Cancer Res 1977; 37: 3042–5.

  2. 2.

    Ebina T, Kohya H, Yamaguchi T, Ishida N. Antimetastatic effect of biological response modifiers in the "double grafted tumor system". Jpn J Cancer Res (Gann) 1986; 77: 1034–42.

  3. 3.

    Ebina T, Kohya H. Antitumor effector mechanism at a distant site in the double grafted tumor system of PSK, a protein-bound polysaccharide preparation. Jpn J Cancer Res (Gann) 1988; 79: 957–64.

  4. 4.

    Ernest PB, Schicchitano R, Underdown BJ, Bienenstock J. Oral immunization and tolerance. In: Heyworth MF, Jones AI, eds. Immunology of the gastrointestinal tract and liver. New York: Raven Press Ltd., 1988: 125–44.

  5. 5.

    Ehlike MJ, Reino JM, Eppolito C, Mihich E. The effect of PS-K, a protein bound polysaccharide, an immune responses against allogenic antigens. Int J Immunopharmac 1983; 5: 35–42.

  6. 6.

    Hanna N, Fidler IJ. Role of natural killer cells in the destruction of circulating tumor emboli. J Natl Cancer Inst 1980; 65: 801–9.

  7. 7.

    Hanna N, Burton RC. Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastasis in vivo. J Immunol 1981; 127: 1754–8.

  8. 8.

    Hattori T, Niimoto M, Nakano A, Oride M, Takiyama W, Nishimawari K. Postoperative long-term immunochemotherapy with Mitomycin-C, PSK and FT-207 in gastric cancer patients. Jpn J Surg 1979; 9: 110–7.

  9. 9.

    Ikuzawa M, Matsunaga K, Nishiyama S, Nakajima S, Kobayashi Y, Andoh Y, Kobayashi A, Ohhara M, Ohmura Y, Wada T, Yoshikumi C. Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin). Int J Immunopharmac, 1988; 10: 415–23.

  10. 10.

    Kamisato JK, Nowakowski Maja. Morphological and biochemical alterations of macrophages produced by a glucan, PSK. Immunopharmacology 1988; 16: 89–96.

  11. 11.

    Kano T, Kumashiro R, Tamada R, Kodama Y, Inokuchi K. Late results of postoperative long term cancer chemotherapy for advanced carcinoma of the stomach. Jpn J Surg 1981; 11: 291–6.

  12. 12.

    Kikuchi Y, Kizawa I, Oomori K, Iwano I, Kita T, Kato K. Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advanced ovarian carcinoma during chemotherapy. Jpn J Cancer Res (Gann) 1988; 79: 125–30.

  13. 13.

    Kitani H, Tsuru S, Oguchi M, Watanabe M, Zinnaka Y. Effect of PSK on interferon production in tumor-bearing mice. J Clin Lab Immunol 1984; 15: 211–4.

  14. 14.

    Mickey DD. Combined therapeutic effects of an im munomodulator, PSK, and chemotherapy with carboquone on rat bladder carcinoma. Cancer Chemother Pharmacol 1985; 15: 54–8.

  15. 15.

    Mizushima Y, Yuhki N, Hosokawa M, Kobayashi H. Diminution of cyclophosphamide-induced suppression of antitumor immunity by an immunomodulator PS-K and combined therapeutic effects of PS-K and cyclophosphamide on transplanted tumor in rats. Cancer Res 1982; 42: 5176–80.

  16. 16.

    Mori H, Mihara M, Teshima K, Uesugi U, Xu Q, Sakamoto O, Koda A. Effect of immunostimulants and antitumor agents on tumor necrosis factor (TNF) production. Int J Immunopharmac 1987; 9: 881–92.

  17. 17.

    Nio Y, Tsuhitani T, Imai S, Shiraishi T, Kan N, Ohgaki K, Tobe T. Immunomodulating effects of oral administration of PSK. II. Its effects on mice with cecal tumors. J Jpn Soc Cancer Ther 1988; 23: 1068–76.

  18. 18.

    Nio Y, Shiraishi T, Tsubono M, Morimoto H, Tseng CC, Imai S, Tobe T.In vitro immunomodulating effects of protein-bound polysaccharide, PSK on peripheral blood, regional nodes and spleen lymphocytes in patients with gastric cancer. Cancer Immunol Immunother 1991; 32: 335–41.

  19. 19.

    Ohno R, Yamada K, Masaoka T, Ohshima T, Amaki I, Hirota Y, Horikoshi N, Horiuchi A, Imai K, Kimura I, Kitajima K, Nakamura H, Nakamura T, Ohta Y, Sakai Y, Tanaka M, Tsubaki K, Uchino H, Ogawa N, Kimura K. A randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in adults using a protein-bound polysaccharide preparation. Cancer Immunol Immunother 1984; 18: 149–54.

  20. 20.

    Sabolovic D, Galoppin L. Effect of a protein bound polysaccharide (PS-K) on the tumor development and infections in splenectomized rats and mice. Int J Immunopharmac 1986; 8: 41–6.

  21. 21.

    Toge T, Yamaguchi Y, Kegoya Y, Baba N, Yanagawa E, Hattori T. Blocking of lymphocyte surface binding sites for the soluble suppressor factor by protein-bound polysaccharide, PSK. Int J Immunopharmac 1989; 11: 9–12.

  22. 22.

    Torisu M. Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Cancer Immunol Immunother 1990; 31: 261–8.

  23. 23.

    Tsukagoshi S, Ohashi F. Protein-bound polysaccharide preparation, PS-K, effective against mouse sarcoma-180 and rat ascites hepatoma AH-13 by oral use. Gann 1974; 65: 557–8.

  24. 24.

    Tsuru S, Nomoto K. Effect of PSK on specific tumor immunity to syngeneic tumor cells. J Clin Lab Immunol 1983; 4: 215–9.

  25. 25.

    Usui S, Urano M, Koike S, Kobayahi Y. Brief communication: effects of PS-K, a protein polysaccharide, on pulmonary metastasies of a C3H mouse squamous cell carcinoma. J Natl Cancer Inst 1976; 56: 185–7.

Download references

Author information

Correspondence to Yoshinori Nio M.D..

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nio, Y., Tsubono, M., Tseng, C. et al. Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer. Biotherapy 4, 117–128 (1992).

Download citation

Key words

  • gastrointestinal cancer
  • NK
  • polysaccharide
  • PSK
  • immunotherapy