Oral administration of soluble -glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice
Oral administration of soluble -glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice
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DOI：
10.1002/ijc.27999
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发表时间：
2013-07-01
影响因子：
6.4
通讯作者：
Nanba, Hiroaki
中科院分区：
文献类型：
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作者：
Masuda, Yuki;Inoue, Hiroko;Nanba, Hiroaki
灰树花D（MD）-级分是从灰树花（一种东方食用菌）中提取的高纯度可溶性葡聚糖.腹膜内（i. p.）已报道注射MD-级分通过增强宿主免疫系统来抑制肿瘤生长。在本研究中，我们证明了MD-组分口服给药以及腹膜内注射可显著抑制小鼠肿瘤模型中的肿瘤生长。经口给药后，MD-组分未以其游离形式转移至血液中，而是被抗原呈递细胞如派伊尔集合淋巴结中存在的巨噬细胞和树突状细胞（DC）捕获。然后将捕获的MD组分转运至脾脏，从而诱导全身免疫应答。我们的研究表明，MD-Fraction通过C型凝集素受体dectin-1途径直接诱导DC成熟。口服给予MD-组分的治疗反应与（i）通过DCs的dectin-1依赖性活化诱导的全身肿瘤抗原特异性T细胞反应，（ii）活化T细胞向肿瘤中的浸润增加和（iii）肿瘤引起的免疫抑制细胞（如调节性T细胞和骨髓源性抑制细胞）数量减少相关。我们的临床前研究表明，MD-Fraction是一种有用的口服治疗药物，用于治疗癌症患者。
Maitake D (MD)-Fraction is a highly purified soluble -glucan derived from Grifola frondosa (an oriental edible mushroom). Intraperitoneal (i.p.) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system. In this study, we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models. After oral administration, MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells (DCs) present in the Peyer's patch. The captured MD-Fraction was then transported to the spleen, thereby inducing the systemic immune response. Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway. The therapeutic response of orally administered MD-Fraction was associated with (i) induced systemic tumor-antigen specific T cell response via dectin-1-dependent activation of DCs, (ii) increased infiltration of the activated T cells into the tumor and (iii) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer.