Guo Siqi, Burcus Niculina I, Hornef James, Jing Yu, Jiang Chunqi, Heller Richard, Beebe Stephen J
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Department of Electrical and Computer Engineering, Batten College of Engineering and Technology, Old Dominion University, Norfolk, VA 23508, USA.
Cancers (Basel). 2018 Jun 27;10(7):217. doi: 10.3390/cancers10070217.
A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to the induction of immune-mediated protection from a second tumor challenge in orthotopic mouse breast and rat liver cancer models. In the Pan02 model, there were insufficient abscopal effects (1/10) and vaccine-like protective effects (1/15) suggesting that NPS-induced immune mechanisms in this model were limited. To evaluate this further, the immune landscape was analyzed. The numbers of both T regulatory cells (Tregs) and myeloid derived suppressor cells (MDSCs) in blood were significantly reduced, but memory (CD44⁺) T-cells were absent. Furthermore, the numbers of Tregs and MDSCs did not reduce in spleens compared to tumor-bearing mice. Very few T-cells, but large numbers of MDSCs were present in the NPS treated tumor microenvironment (TME). The number of dendritic cells in the TME was increased and multiple activation markers were upregulated following NPS treatment. Overall, NPS treatments used here are effective for pancreatic tumor ablation, but require further optimization for induction of immunity or the need to include effective combinational NPS therapeutic strategy for pancreatic cancer.
胰腺癌是一种预后极差的恶性肿瘤。目前的标准治疗方法对晚期胰腺癌的疗效甚微。在本研究中，我们在同基因小鼠Pan02胰腺癌模型中评估了纳米脉冲刺激（NPS）作为胰腺癌局部治疗的效果，并对免疫谱的相应变化进行了表征。单次NPS治疗要么使肿瘤完全消退，要么延长了部分肿瘤消退动物的总生存期。虽然这非常令人鼓舞，但我们也探讨了这种局部消融效应是否也能导致免疫刺激，正如在原位小鼠乳腺癌和大鼠肝癌模型中观察到的那样，NPS可诱导对第二次肿瘤攻击的免疫介导保护。在Pan02模型中，远隔效应（1/10）和疫苗样保护效应（1/15）不足，这表明该模型中NPS诱导的免疫机制有限。为了进一步评估这一点，我们分析了免疫格局。血液中调节性T细胞（Tregs）和髓源性抑制细胞（MDSCs）的数量均显著减少，但记忆性（CD44⁺）T细胞缺失。此外，与荷瘤小鼠相比，脾脏中Tregs和MDSCs的数量并未减少。在NPS处理的肿瘤微环境（TME）中，T细胞很少，但MDSCs数量众多。NPS处理后，TME中树突状细胞的数量增加，多种激活标志物上调。总体而言，这里使用的NPS治疗对胰腺肿瘤消融有效，但需要进一步优化以诱导免疫，或者需要纳入有效的NPS联合治疗策略来治疗胰腺癌。
