College of Pharmacy and Medical Research Center (CICT), Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Cancer Lett. 2011 Dec 27;313(2):226-34. doi: 10.1016/j.canlet.2011.09.009. Epub 2011 Sep 17.
The clinical efficacy of dendritic cell (DC) vaccine in cancer patients has been unsatisfactory due, at least in part, to the deficiency of maturation and impaired migration of ex vivo generated DCs to the draining lymph nodes. To solve this problem, we used angelan, a natural TLR4 ligand, to enhance the maturation and migration of DCs. Angelan increased the expression of MHC-I/II, CD80, and CD86, DC maturation markers, through the NF-κB pathway. This compound also increased CCR7 expression in DCs through NF-κB and p38 pathway and enhanced their migration against CCL19, which is a key chemokine that guides DCs into lymph nodes. We also showed that angelan enhanced in vivo DC homing from tissues to draining lymph nodes. When treated to DCs in vitro and vivo, angelan increased antitumor activity of DCs in B16F10 syngeneic tumor model. Taken together, the present data suggest that a natural TLR4 ligand might be helpful for overcoming the disadvantages of DC-based cancer therapy, such as impaired maturation and poor migration in cancer patients.
树突状细胞（DC）疫苗在癌症患者中的临床疗效并不令人满意，这至少部分是由于体外生成的 DC 成熟和向引流淋巴结迁移的缺陷所致。为了解决这个问题，我们使用 angelan（一种天然的 TLR4 配体）来增强 DC 的成熟和迁移。Angelan 通过 NF-κB 途径增加了 MHC-I/II、CD80 和 CD86（DC 成熟标志物）的表达。该化合物还通过 NF-κB 和 p38 途径增加了 DC 中 CCR7 的表达，并增强了它们对趋化因子 CCL19 的迁移能力，CCL19 是一种引导 DC 进入淋巴结的关键趋化因子。我们还表明，angelan 增强了体内 DC 从组织向引流淋巴结的归巢。当在体外和体内处理 DC 时，angelan 增强了 B16F10 同基因肿瘤模型中 DC 的抗肿瘤活性。总之，这些数据表明，天然的 TLR4 配体可能有助于克服基于 DC 的癌症治疗的缺点，例如癌症患者中 DC 成熟和迁移不良。
