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在临床前免疫疗法实验中研究瘤宿主反应动态,使用逐步数学建模策略

Angela M Jarrett¹, Patrick N Song², Kirsten Reeves³

¹Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, USA; Livestrong Cancer Institutes, The University of Texas at Austin, USA.

Mathematical biosciences

|November 6, 2023

概括

数学模型显示,癌症免疫疗法失败与随着时间的推移免疫反应的减弱有关. 这种方法量化瘤的攻击性和免疫细胞的功能,以预测治疗结果.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
数学生物学数学生物学

背景情况:

针对PD1和CTLA4的免疫疗法在不同瘤中显示出不同的疗效.
了解免疫疗法反应和失败的动态对于改善癌症治疗至关重要.

研究的目的:

开发一个数学建模策略来量化免疫治疗的成功和失败.
研究免疫疗法失败的生物驱动因素,包括瘤血管结构,免疫反应和药物剂量.

主要方法:

对大肠直肠癌和乳腺癌的小鼠模型应用了一个逐步的数学建模策略.
利用纵向瘤体积数据和指数增长模型来定义反应组.
集成的[18F]化森尼达 (FMISO) -正电子发射断层扫描 (PET) 数据以模拟随时间推移的瘤缺氧和血管质量.
扩展模型,包括免疫反应和药物剂量,以系统地调查假设.

主要成果:

通过对PET数据进行数学模型校准,量化瘤血管系统恶化的生物驱动因素.
模型模拟确定了非响应性瘤中免疫反应分数的升高.
结果表明,免疫治疗失败与功能性免疫反应有关,这种功能性免疫反应随着时间的推移而减弱.

结论:

实验数学方法使得从单独的数据中无法辨别系统动态的探索成为可能.
确定了导致免疫疗法失败的关键因素,包括瘤的攻击性,免疫疲劳和免疫细胞功能.
提供了一个框架,用于生成关于免疫治疗免疫反应的实验性可测试预测.

关键词:

计算的计算计算的计算 E0771 是一个很好的标签.这就是FMISO-PET.氧气过低是因为缺氧.图像成像是一种成像.免疫反应的免疫反应.MC3838 是一个很棒的游戏.

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相关概念视频

Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.