Pancreatic adenocarcinoma (PAC) has a poor prognosis. One treatment approach, investigated here, is to reinforce antitumor immunity. Dendritic cells (DCs) are essential for the development and regulation of adaptive host immune responses against tumors. A major role for DCs may be as innate tumoricidal effector cells. We explored the efficacy of vaccination with immature (i)DCs, after selecting optimal conditions for generating immunostimulatory iDCs. We used two models, C57BL/6Jrj mice with ectopic tumors induced by the PAC cell line, Panc02, and genetically engineered (KIC) mice developing PAC. Therapeutic iDC-vaccination resulted in a significant reduction in tumor growth in C57BL/6Jrj mice and prolonged survival in KIC mice. Prophylactic iDC-vaccination prevented subcutaneous tumor development. These protective effects were long-lasting in Panc02-induced tumor development, but not in melanoma. iDC-vaccination impacted the immune status of the hosts by greatly increasing the percentage of CD8+ T-cells, and natural killer (NK)1.1+ cells, that express granzyme B associated with Lamp-1 and IFN-γ. Efficacy of iDC-vaccination was CD8+ T-cell-dependent but NK1.1+ cell-independent. We demonstrated the ability of DCs to produce peroxynitrites and to kill tumor cells; this killing activity involved peroxynitrites. Altogether, these findings make killer DCs the pivotal actors in the beneficial clinical outcome that accompanies antitumor immune responses. We asked whether efficacy can be improved by combining DC-vaccination with the FOLFIRINOX regimen. Combined treatment significantly increased the lifespan of KIC mice with PAC. Prolonged treatment with FOLFIRINOX clearly augmented this beneficial effect. Combining iDC-vaccination with FOLFIRINOX may therefore represent a promising therapeutic option for patients with PAC.

中文翻译：

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基于树突细胞的疫苗接种：未成熟的树突细胞针对胰腺腺癌的强大资源。

胰腺腺癌（PAC）的预后较差。本文研究的一种治疗方法是增强抗肿瘤免疫力。树突状细胞（DC）对于发展和调节针对肿瘤的适应性宿主免疫反应至关重要。DC的主要作用可能是作为先天的肿瘤效应细胞。在选择产生免疫刺激性iDC的最佳条件后，我们探讨了未成熟（i）DC的疫苗接种的功效。我们使用了两种模型，即具有由PAC细胞系Panc02诱导的异位肿瘤的C57BL / 6Jrj小鼠和开发PAC的基因工程（KIC）小鼠。iDC疫苗的治疗导致C57BL / 6Jrj小鼠的肿瘤生长显着减少，而KIC小鼠的生存期延长。预防性iDC疫苗预防了皮下肿瘤的发展。这些保护作用在Panc02诱导的肿瘤发展中持久，但在黑素瘤中却没有。iDC疫苗通过大大增加CD8 + T细胞和天然杀伤（NK）1.1+细胞的百分比，影响了宿主的免疫状态，这些细胞表达与Lamp-1和IFN-γ相关的颗粒酶B。iDC疫苗接种的功效是CD8 + T细胞依赖性的，而与NK1.1 +细胞无关的。我们证明了DC产生过氧亚硝酸盐并杀死肿瘤细胞的能力。这种杀死活性涉及过氧亚硝酸盐。总而言之，这些发现使杀伤性DC成为伴随抗肿瘤免疫反应的有益临床结果中的关键角色。我们问是否可以通过将直流疫苗与FOLFIRINOX方案相结合来提高疗效。联合治疗显着增加了PAC致KIC小鼠的寿命。FOLFIRINOX的长期治疗明显增强了这种有益效果。因此，将iDC疫苗与FOLFIRINOX联合使用可能代表PAC患者有希望的治疗选择。