Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived beta-glucans

作者：Qi Chunjian; Cai Yihua; Gunn Lacey; Ding Chuanlin; Li Bing; Kloecker Goetz; Qian Keqing; Vasilakos John; Saijo Shinobu; Iwakura Yoichiro; Yannelli John R; Yan Jun^*

来源：Blood, 2011, 117(25): 6825-6836.

DOI：10.1182/blood-2011-02-339812

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. (Blood. 2011;117(25):6825-6836)

• 出版日期2011-6-23
• 单位南京医科大学; 河北医科大学