The role of tumor activation and inhibition with saturation effects in a mathematical model of tumor and immune system interactions undergoing oncolytic viral therapy
The role of tumor activation and inhibition with saturation effects in a mathematical model of tumor and immune system interactions undergoing oncolytic viral therapy
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DOI：
10.1002/mma.9152
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发表时间：
2023-03-02
影响因子：
2.9
通讯作者：
Jang，Sophia R-J
中科院分区：
文献类型：
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作者：
Vithanage，G. V. R. K.;Wei，Hsiu-Chuan;Jang，Sophia R-J
我们提出并研究了一个通过溶瘤病毒疗法（OVT）控制癌症与免疫系统之间相互作用的数学模型，其中癌细胞可以在饱和的同时激活和抑制免疫细胞。当不应用该疗法时，它表明，相互作用可以支持最多三个双曲型正平衡，其中两个总是渐近稳定的，另一个是鞍点。可达到的稳定肿瘤负荷可以是小的或大的，这取决于初始肿瘤大小。我们通过证明对应于OVT失效的无病毒平衡点的全局渐近稳定性来分析完整模型。基于模型参数的充分条件下，该模型是一致持久的。使用Koujima等人进行的人类胰腺癌小鼠模型验证了所提出的系统。全局敏感性分析表明，肿瘤介导的杀伤率和免疫细胞耗竭对肿瘤进展和治疗成功至关重要。数值分岔分析表明，鞍点可以用来估计OVT根除的最大肿瘤负荷。此外，免疫抑制微环境可以增强病毒治疗功效。
We propose and study a mathematical model governing interactions between cancer and immune system with an oncolytic viral therapy (OVT), wherein cancer cells can activate and inhibit immune cells simultaneously with saturations. When the therapy is not applied, it is shown that the interaction can support at most three hyperbolic positive equilibria where two of them are always asymptotically stable and the other is a saddle point. The reachable stable tumor burden can be either small or large depending on initial tumor size. We analyze the full model by proving global asymptotic stability of the virus‐free equilibrium that corresponds to OVT failure. Sufficient conditions based on model parameters are derived under which the model is uniformly persistent. The proposed system is validated using a mouse model of human pancreatic cancer carried out by Koujima et al. Global sensitivity analysis indicates that the rates of tumor‐mediated killing and immune cell exhaustion are critical for tumor progression and therapy success. Numerical bifurcation analysis reveals that the saddle point can be utilized to estimate the maximum tumor load for eradication by OVT. Moreover, an immunosuppressive microenvironment may enhance viral therapy efficacy.