Orally administered particulate beta-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer.
Orally administered particulate beta-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer.
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DOI：
10.1158/1078-0432.ccr-10-0820
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Yan J
中科院分区：
文献类型：
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作者：
Li B;Cai Y;Qi C;Hansen R;Ding C;Mitchell TC;Yan J
几个世纪以来，β-葡聚糖的有益特性已得到认可。他们提出的癌症治疗中的作用机制通过刺激巨噬细胞和引发先天性中性粒细胞补体受体3（CR 3）来引发iC 3b调理的肿瘤细胞的CR 3依赖性细胞毒性而发生。目前的研究是调查β-葡聚糖治疗是否对抗肿瘤适应性T细胞反应有任何影响。我们首先研究了口服颗粒酵母衍生β-葡聚糖的运输及其与捕获肿瘤物质的树突状细胞（DC）的相互作用。将抗原特异性T细胞过继转移到受体小鼠中，以确定口服β-葡聚糖治疗是否诱导增强的T细胞应答。采用刘易斯肺癌和RAM-S淋巴瘤模型，观察口服β-葡聚糖的治疗作用。进一步的机制研究，包括肿瘤浸润性T细胞和细胞因子谱内的肿瘤环境进行了测定。口服颗粒β-葡聚糖进入脾脏和淋巴结，激活DC，在体内捕获垂死的肿瘤细胞，导致抗原特异性CD 4和CD 8 T细胞的扩增和激活。此外，经β-葡聚糖治疗后，肿瘤浸润性T细胞的IFN-γ产生和CTL应答显著增强，最终导致肿瘤负荷显著降低。此外，β-葡聚糖处理的肿瘤具有显著更多的DC浸润，具有活化的表型，并且在肿瘤微环境中具有显著水平的Th 1偏向的细胞因子。这些数据突出了酵母衍生的β-葡聚糖桥接先天性和适应性抗肿瘤免疫的能力，并表明其可用作肿瘤免疫治疗的佐剂。
The beneficial properties of β-glucans have been recognized for centuries. Their proposed mechanisms of action in cancer therapy occur via stimulation of macrophages and priming of innate neutrophil complement receptor 3 (CR3) for eliciting CR3-dependent cellular cytotoxicity of iC3b-opsonized tumor cells. The current study is to investigate whether β-glucan therapy has any impact on anti-tumor adaptive T cell responses. We first examined the trafficking of orally administered particulate yeast-derived β-glucan and its interaction with dendritic cells (DCs) that captured tumor materials. Antigen-specific T cells were adoptively transferred into recipient mice to determine whether oral β-glucan therapy induces augmented T cell responses. Lewis lung carcinoma and RAM-S lymphoma models were used to test oral β-glucan therapeutic effect. Further mechanistic studies including tumor-infiltrating T cells and cytokine profiles within the tumor milieu were determined. Orally administered particulate β-glucan trafficked into spleen and lymph nodes and activated DCs that captured dying tumor cells in vivo, leading to the expansion and activation of antigen-specific CD4 and CD8 T cells. In addition, IFN-γ production of tumor-infiltrating T cells and CTL responses were significantly enhanced upon β-glucan treatment, which ultimately resulted in significantly reduced tumor burden. Moreover, β-glucan-treated tumors had significantly more DC infiltration with the activated phenotype and significant levels of Th1-biased cytokines within the tumor microenvironment. These data highlight the ability of yeast-derived β-glucan to bridge innate and adaptive anti-tumor immunity and suggest that it can be used as an adjuvant for tumor immunotherapy.