Advertisement

Cancer Immunology, Immunotherapy

, Volume 55, Issue 10, pp 1258–1266 | Cite as

Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses

  • Yunfei Gao
  • Dongqing Zhang
  • Buxiang Sun
  • Hajime Fujii
  • Ken-Ichi Kosuna
  • Zhinan Yin
Original Article

Abstract

Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4+ and CD8+ T cells, increased the number of tumor Ag-specific CD8+ T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-γ producing CD8+ T cells. Interestingly, AHCC treatment also showed increased cell number of NK and γδ T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.

Keywords

Nutrition food T cells Tumor immunity IFN-γ Tumor therapy 

Abbreviations

CFSE

5-(and –6) Carboxyfluorescein diacetate, succinimidyl ester

AHCC

Active hexose correlated compound

Notes

Acknowledgements

We thank Dr. Kim Bottomly from Yale Immunobiology for providing C57BL/6 OT-1 and OT-II transgenic mice. We thank Dr. Fotios Koumpouras and Dr. Bohdan Harvey for critical review of the manuscript. This work was supported by an Arthritis Foundation Investigator Award, NIH (NIAMS) K01 AR 02188 and NIH (NIAID) R01 (R01 AI56219) grant (Z.Y.), and partially supported by the Amino Up, Japan (Z.Y). D.Z. is supported by National Science Foundation of China (No. 30471593), Shanghai Leading Academic Discipline Project (T 0206). Authors from Yale have no financial conflict of interest.

References

  1. 1.
    Wakame K (1999) Protective effects of active hexose correlated compound (AHCC) on the onset of diabetes induced by Streptozotocin in the rat. Biomed Res 20:145–152Google Scholar
  2. 2.
    Ghoneum M, Wimbley M, Salem F, Mcklain A, Attallah N, Gill G (1995) Immunomodulatory and anticancer effects of active hemicellulose compound (AHCC). Int J Immunother 11:23–28Google Scholar
  3. 3.
    Kidd PM (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 5:4–27PubMedGoogle Scholar
  4. 4.
    Sun B, Wakame K, Mukoda T, Toyoshima A, Kana-zawa T, Kosuna K (1997) Protective effects of AHCC on carbon tetrachloride induced liver injury in mice. Nat Med 51:310–315Google Scholar
  5. 5.
    Burikhanov RB, Wakame K, Igarashi Y, Wang S, Matsuzaki S (2000) Suppressive effect of active hexose correlated compound (AHCC) on thymic apoptosis induced by dexamethasone in the rat. Endocr Regul 34:181–188PubMedGoogle Scholar
  6. 6.
    Shuyi Wang, Ichimura K, Wakame K (2001) Preventive effects of active hexose correlated compound (AHCC) on oxidative stress induced by ferric nitrilotriacetate in the Rat. Dokkyo J Med Sci 28:745–752Google Scholar
  7. 7.
    Ye SF, Wakame K, Ichimura K, Matsuzaki S (2004) Amelioration by active hexose correlated compound of endocrine disturbances induced by oxidative stress in the rat. Endocr Regul 38:7–13PubMedGoogle Scholar
  8. 8.
    Matsushita K, Kuramitsu Y, OhiroY, Obara M, Kobayashi M, Li YQ, Hosokawa M (1998) Combination therapy of active hexose correlated compound plus UFT significantly reduces the metastasis of rat mammary adenocarcinoma. Anticancer Drugs 9:343–350PubMedCrossRefGoogle Scholar
  9. 9.
    Mamdooh G, Phyllis P, Yasuo N, Mabrouk G, Gus G (1992) Enhancement of NK cell activity in cancer patients by active hemicellulose compound (AHCC). In: Adjuvant Nutrition in Cancer Treatment Symposium, Tulsa, OKGoogle Scholar
  10. 10.
    Yagita A, Matsuzaki S, Wakasugi S, Sukegawa Y (2002) H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts. In Vivo 16:49–54PubMedGoogle Scholar
  11. 11.
    Ye SF, Ichimura K, Wakame K, Ohe M (2003) Suppressive effects of active hexose correlated compound on the increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress. Life Sci 74:593–602CrossRefPubMedGoogle Scholar
  12. 12.
    Aviles H, Belay T, Vance M, Sun B, Sonnenfeld G (2004) Active hexose correlated compound enhances the immune function of mice in the hindlimb-unloading model of spaceflight conditions. J Appl Physiol 97:1437–1444CrossRefPubMedGoogle Scholar
  13. 13.
    Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFN gamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111CrossRefPubMedGoogle Scholar
  14. 14.
    Gao Y, Yang W, Pan M, Scully E, Girardi M, Augenlicht LH, Craft J, Yin Z (2003) Gamma delta T cells provide an early source of interferon gamma in tumor immunity. J Exp Med 198:433–442CrossRefPubMedGoogle Scholar
  15. 15.
    Hanson HL, Donermeyer DL, Ikeda H, White JM, Shankaran V, Old LJ, Shiku H, Schreiber RD, Allen PM (2000) Eradication of established tumors by CD8+ T cell adoptive immunotherapy. Immunity 13:265–276CrossRefPubMedGoogle Scholar
  16. 16.
    Dobrzanski MJ, Reome JB, Dutton RW (1999) Therapeutic effects of tumor-reactive type 1 and type 2 CD8+ T cell subpopulations in established pulmonary metastases. J Immunol 162:6671–6680PubMedGoogle Scholar
  17. 17.
    Strome SE, Voss S, Wilcox R, Wakefield TL, Tamada K, Flies D, Chapoval A, Lu J, Kasperbauer JL, Padley D, Vile R, Gastineau D, Wettstein P, Chen L (2002) Strategies for antigen loading of dendritic cells to enhance the antitumor immune response. Cancer Res 62:1884–1889PubMedGoogle Scholar
  18. 18.
    Yin Z, Zhang DH, Welte T, Bahtiyar G, Jung S, Liu L, Fu XY, Ray A, Craft J (2000) Dominance of IL-12 over IL-4 in gamma delta T cell differentiation leads to default production of IFN-gamma: failure to down-regulate IL-12 receptor beta 2-chain expression. J Immunol 164:3056–3064PubMedGoogle Scholar
  19. 19.
    Gao Y, Tao J, Li MO, Zhang D, Chi H, Henegariu O, Kacch SM, Davis RJ, Flavell RA, Yin Z (2005) JNK1 is essential for CD8+ T cell-mediated tumor immune surveillance. J Immunol 175(9):5783–5789PubMedGoogle Scholar
  20. 20.
    Gorelik L, Flavell RA (2001) Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 7:1118–1122CrossRefPubMedGoogle Scholar
  21. 21.
    Ikeda H, Old LJ, Schreiber RD (2002) The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev 13:95–109CrossRefPubMedGoogle Scholar
  22. 22.
    deVere White RW, Hackman RM, Soares SE, Beckett LA, Li Y, Sun B (2004) Effects of a genistein-rich extract on PSA levels in men with a history of prostate cancer Urology 63:259–263Google Scholar
  23. 23.
    deVere White RW, Hackman RM, Soares SE, Beckett LA, Sun B (2002) Effects of a mushroom mycelium extract on the treatment of prostate cancer. Urology 60:640–644CrossRefPubMedGoogle Scholar
  24. 24.
    Dunn GP, Old LJ, Schreiber RD, Bruce AT, Ikeda H (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148CrossRefPubMedGoogle Scholar
  25. 25.
    Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111CrossRefPubMedGoogle Scholar
  26. 26.
    Carding SR, Egan PJ (2002) Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2:336–345CrossRefPubMedGoogle Scholar
  27. 27.
    Yin Z, Chen C, Szabo SJ, Glimcher LJ, Ray A, Craft J (2002) T-Bet expression and failure of GATA-3 cross-regulation lead to default production of IFN-gamma by gammadelta T cells. J Immunol 168:1566–1571PubMedGoogle Scholar
  28. 28.
    Ghoneum M, NY, Torabi M, Gill G, Wojdani A (1992) Active hemicellulose compound (AHCC) enhance NK cell activity of aged mice in vivo. FASEB J 6:A1213 (Abstract)Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Yunfei Gao
    • 1
  • Dongqing Zhang
    • 2
  • Buxiang Sun
    • 3
  • Hajime Fujii
    • 3
  • Ken-Ichi Kosuna
    • 3
  • Zhinan Yin
    • 1
  1. 1.Section of Rheumatology, Department of MedicineYale School of MedicineNew HavenUSA
  2. 2.Shanghai Institute of ImmunologyShanhai Jiaotong University School of MedicineShanhaiChina
  3. 3.R&D DivisionAmino Up Chemical Co., LtdSapporoJapan

Personalised recommendations