Other
12 Authors
- Qian K,
- Kloecker G,
- Yannelli JR,
- Gunn L,
- Cai Y,
- Vasilakos J,
- Li B,
- Saijo S,
- Qi C,
- Ding C,
- Yan J,
- Iwakura Y
First Author | Qi C | Year | 2011 |
Journal | Blood | Volume | 117 |
Issue | 25 | Pages | 6825-36 |
PubMed ID | 21531981 | Mgi Jnum | J:174813 |
Mgi Id | MGI:5141198 | Doi | 10.1182/blood-2011-02-339812 |
Citation | Qi C, et al. (2011) Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived beta-glucans. Blood 117(25):6825-36 |
abstractText | beta-glucans have been reported to function as a potent adjuvant to stimulate innate and adaptive immune responses. However, beta-glucans from different sources are differential in their structure, conformation, and thus biologic activity. Different preparations of beta-glucans, soluble versus particulate, further complicate their mechanism of action. Here we show that yeast-derived particulate beta-glucan activated dendritic cells (DCs) and macrophages via a C-type lectin receptor dectin-1 pathway. Activated DCs by particulate beta-glucan promoted Th1 and cytotoxic T-lymphocyte priming and differentiation in vitro. Treatment of orally administered yeast-derived particulate beta-glucan elicited potent antitumor immune responses and drastically down-regulated immunosuppressive cells, leading to the delayed tumor progression. Deficiency of the dectin-1 receptor completely abrogated particulate beta-glucan-mediated antitumor effects. In contrast, yeast-derived soluble beta-glucan bound to DCs and macrophages independent of the dectin-1 receptor and did not activate DCs. Soluble beta-glucan alone had no therapeutic effect but significantly augmented antitumor monoclonal antibody-mediated therapeutic efficacy via a complement activation pathway but independent of dectin-1 receptor. These findings reveal the importance of different preparations of beta-glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials. |