Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway.
PLoS One. 2012;7(2):e31217. doi: 10.1371/journal.pone.0031217. Epub 2012 Feb 21.
Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.
树突状细胞（DC）在治疗性癌症免疫疗法中必须能够刺激 T 细胞，从而产生能够有效靶向癌细胞的免疫反应。其中一个关键的障碍是在成熟 DC 时缺乏 IL-12p70 的产生，这可以通过使用细菌制剂 OK432（商品名 Picibanil）来成熟细胞来解决。为了确定 OK432 刺激 DC 的机制，我们研究了不同 TLR 的贡献，以检查它们在 IL-12p70 产生中的参与。通过结合 TLR 信号转导的不同抑制剂，我们在这里证明 TLR3 负责 OK432 诱导的 DC 中 IL-12p70 的产生。此外，我们的数据表明，TLR3 刺激引发 IL-12p70 分泌的配体对蛋白酶和部分 RNAse 处理敏感。像 OK432 这样的细菌化合物能够激活人 DC 中的 TLR3 途径是一个新发现。OK432 表现出诱导 IL-12p70 产生的关键能力，这在基于 DC 的癌症免疫疗法中具有重要意义。
