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Differential Pathways Regulating Innate and Adaptive Anti-tumor Immune Responses by Particulate and Soluble Yeast-derived Beta-Glucans

Blood 2011 117:6825-6836; doi:10.1182/blood-2011-02-339812

Chunjian Qi 1, 2 *, Yihua Cai 1 *, Lacey Gunn 1,3, Chuanlin Ding 1, Bing Li 1, 3, Goetz Kloecker 1, Keqing Qian 2, John Vasilakos 4, Shinobu Saijo 5, Yoichiro Iwakura 6, John R. Yannelli 7, Jun Yan 1, 3

  1. Division of Hematology/Oncology, Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, U.S.A.
  2. Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People’s Hospital, Changzhou 213003, China
  3. Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, U.S.A.
  4. Biothera, Eagan, MN, U.S.A.
  5. Division of Molecular Immunology, Medical Mycology Research Center, Chiba University 1-8-1 Inohana, Chui-ku, Chiba 260-8673, Japan.
  6. Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
  7. Department of Microbiology and Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, KY, U.S.A.

*These authors contributed equally to this work.

β-Glucans have been reported to function as a potent adjuvant to stimulate innate and adaptive immune responses. However, β-glucans from different sources are differential in their structure, conformation, and thus biological activity. Different preparations of β-glucans, soluble versus particulate, further complicate their mechanism of action. Here we show that yeast-derived particulate β-glucan activated dendritic cells (DCs) and macrophages via C-type lectin receptor dectin-1 pathway. Activated DCs by particulate β-glucan promoted Th1 and cytotoxic Tlymphocyte priming and differentiation in vitro. Treatment of orally administrated yeast-derived particulate β-glucan elicited potent anti-tumor immune responses and drastically downregulated immunosuppressive cells, leading to the delayed tumor progression. Deficiency of dectin-1 receptor completely abrogated particulate β-glucan-mediated anti-tumor effects. In contrast, yeast-derived soluble β-glucan bound to DCs and macrophages independent of dectin-1 receptor and did not activate DCs. Soluble β-glucan alone had no therapeutic effect but significantly augmented anti-tumor mAb-mediated therapeutic efficacy via complement activation pathway but independent of dectin-1 receptor. These findings reveal the importance of different preparations of β-glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials.

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Published at wellmune.com on 27 June 2011

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