Department of Immunology, Zunyi Medical College, Guizhou, China.
Immunol Lett. 2012 Feb 29;142(1-2):55-63. doi: 10.1016/j.imlet.2011.12.006. Epub 2012 Jan 11.
Our previous data showed that CpG-ODNs could significantly enhance the anti-tumor efficacy of adoptively cell transfer (ACT), which was closely correlated to accumulation of Th17 cells in tumor mass. Here we further investigated that CpG-ODNs had no significant effect on the migration and proliferation capacity of Th17 cells in tumor mass. Instead, we showed that CpG-ODNs could induce the differentiation of Th17 cells via dendritic cells (DCs) in tumor infiltrating lymphocytes (TILs). Notably, we found that plasmacytoid dendritic cells (pDCs), but not myeloid dendritic cells (mDCs), were responsible for the Th17 differentiation induced by CpG-ODNs via IL-6, TGF-β and IFN-α in vitro. Finally, we revealed that CpG-ODNs could stimulate pDCs to induce the differentiation of Th17 cells in vivo, which subsequently reduced the tumor size and prolonged the survival of tumor bearing nude mice. These data provided a novel insight into the mechanism of anti-tumor efficacy of CpG-ODNs based therapeutic strategy.
我们先前的数据表明，CpG-ODN 可显著增强过继细胞转移（ACT）的抗肿瘤疗效，这与肿瘤组织中 Th17 细胞的积累密切相关。在此，我们进一步研究发现 CpG-ODN 对肿瘤组织中 Th17 细胞的迁移和增殖能力没有显著影响。相反，我们表明 CpG-ODN 可通过肿瘤浸润淋巴细胞（TIL）中的树突状细胞（DC）诱导 Th17 细胞分化。值得注意的是，我们发现 CpG-ODN 通过 IL-6、TGF-β 和 IFN-α 在体外诱导 Th17 分化主要依赖于浆细胞样树突状细胞（pDC），而非髓样树突状细胞（mDC）。最后，我们揭示了 CpG-ODN 可在体内刺激 pDC 诱导 Th17 细胞分化，进而减少肿瘤大小并延长荷瘤裸鼠的存活时间。这些数据为 CpG-ODN 基于治疗策略的抗肿瘤疗效机制提供了新的见解。
