论文标题
一种探索T细胞浸润对抗肿瘤免疫反应的影响的混合离散核模型建模方法
A hybrid discrete-continuum modelling approach to explore the impact of T-cell infiltration on anti-tumour immune response
论文作者
论文摘要
我们为肿瘤细胞和细胞毒性T细胞之间的相互作用动力学提供了空间混合离散 - 胞源建模框架，该框架在针对肿瘤的免疫反应中起关键作用。在此框架中，将肿瘤细胞和T细胞建模为单个药物，而驱动T细胞向肿瘤趋化运动的趋化因子将其建模为连续体。我们正式得出了该模型的连续性对应物，该模型由一个耦合系统给出，该系统包含肿瘤细胞密度密度的全差分方程，T细胞密度的部分微分方程以及趋化因子浓度的部分微分方程。我们报告了混合模型的计算结果，并表明它们之间存在出色的定量一致性和相应的连续体模型的数值解决方案。这些结果阐明了T细胞中不同水平浸润到肿瘤的机制，并阐明T细胞浸润如何形成抗肿瘤的免疫反应。此外，为了提出一个概念证明，即可以利用连续性模型的计算效率，可以进行广泛的数值模拟，我们研究了T细胞浸润对肿瘤细胞对不同类型的抗癌免疫疗法的反应的影响。
We present a spatial hybrid discrete-continuum modelling framework for the interaction dynamics between tumour cells and cytotoxic T cells, which play a pivotal role in the immune response against tumours. In this framework, tumour cells and T cells are modelled as individual agents while chemokines that drive the chemotactic movement of T cells towards the tumour are modelled as a continuum. We formally derive the continuum counterpart of this model, which is given by a coupled system that comprises an integro-differential equation for the density of tumour cells, a partial differential equation for the density of T cells, and a partial differential equation for the concentration of chemokines. We report on computational results of the hybrid model and show that there is an excellent quantitative agreement between them and numerical solutions of the corresponding continuum model. These results shed light on the mechanisms that underlie the emergence of different levels of infiltration of T cells into the tumour and elucidate how T-cell infiltration shapes anti-tumour immune response. Moreover, to present a proof of concept for the idea that, exploiting the computational efficiency of the continuum model, extensive numerical simulations could be carried out, we investigate the impact of T-cell infiltration on the response of tumour cells to different types of anti-cancer immunotherapy.
