Frascoli Federico, Flood Emelie, Kim Peter S
Faculty of Science, Engineering and Technology, Department of Mathematics, Swinburne University of Technology, Melbourne, Victoria, Australia.
School of Applied Sciences, RMIT University, Melbourne, Victoria, Australia.
Math Med Biol. 2017 Jun 1;34(2):215-240. doi: 10.1093/imammb/dqw004.
We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction.
我们提出了一个三维模型，用于模拟抗癌T细胞对小型、无血管的早期肿瘤的反应动力学。肿瘤部位的相互作用通过基于主体的模型（ABM）来描述，而淋巴结中的免疫细胞动力学则被建模为一个延迟微分方程（DDE）系统。我们将这些不同的方法结合成一个两室混合ABM-DDE系统，以捕捉T细胞对肿瘤的反应。在肿瘤部位的ABM中，肿瘤细胞的运动通过有效的物理力进行建模，特别关注细胞间的粘附特性和不同水平的肿瘤细胞运动性，从而考虑到癌细胞扩散和形成簇的能力。我们考虑了在一系列与肿瘤细胞运动性、细胞间粘附强度和生长速率相关的参数下免疫反应的有效性。我们还研究了结果对肿瘤细胞分布的依赖性。低肿瘤细胞运动性通常是在复发前成功根除肿瘤的良好指标，而高运动性几乎总是导致复发和肿瘤逃逸。一般来说，细胞间粘附对预后的影响取决于肿瘤细胞运动性的水平，粘附和运动性之间往往存在不可预测的交叉影响，这可能导致违反直觉的效果。就整体肿瘤形状和结构而言，不同大小簇中癌细胞的空间分布已显示与灭绝可能性密切相关。
