Peng Huiming, Zhao Weiling, Tan Hua, Ji Zhiwei, Li Jingsong, Li King, Zhou Xiaobo
Division of Radiologic Sciences - Center for Bioinformatics and Systems Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.
Sci Rep. 2016 Feb 12;6:21599. doi: 10.1038/srep21599.
Prostate immune system plays a critical role in the regulation of prostate cancer development regarding androgen-deprivation therapy (ADT) and/or immunotherapy (vaccination). In this study, we developed a mathematical model to explore the interactions between prostate tumor and immune microenvironment. This model was used to predict treatment outcomes for prostate cancer with ADT, vaccination, Treg depletion and/or IL-2 neutralization. Animal data were used to guide construction, parameter selection, and validation of our model. Our analysis shows that Treg depletion and/or IL-2 neutralization can effectively improve the treatment efficacy of combined therapy with ADT and vaccination. Treg depletion has a higher synergetic effect than that from IL-2 neutralization. This study highlights a potential therapeutic strategy in effectively managing prostate tumor growth and provides a framework of systems biology approach in studying tumor-related immune mechanism and consequent selection of therapeutic regimens.
前列腺免疫系统在雄激素剥夺疗法（ADT）和/或免疫疗法（疫苗接种）对前列腺癌发展的调控中起着关键作用。在本研究中，我们建立了一个数学模型来探索前列腺肿瘤与免疫微环境之间的相互作用。该模型用于预测ADT、疫苗接种、调节性T细胞（Treg）耗竭和/或白细胞介素-2（IL-2）中和治疗前列腺癌的疗效。动物数据用于指导我们模型的构建、参数选择和验证。我们的分析表明，Treg耗竭和/或IL-2中和可有效提高ADT与疫苗接种联合治疗的疗效。Treg耗竭比IL-2中和具有更高的协同效应。本研究突出了一种有效控制前列腺肿瘤生长的潜在治疗策略，并提供了一个系统生物学方法框架，用于研究肿瘤相关免疫机制以及后续治疗方案的选择。
