Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response
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DOI：
10.1155/2020/4834165
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发表时间：
2020-08
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影响因子：
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通讯作者：
Zhongtao Yang;Cuihong Yang;Yueping Dong;Y. Takeuchi
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作者：
Zhongtao Yang;Cuihong Yang;Yueping Dong;Y. Takeuchi
抗肿瘤的免疫系统通过一个复杂的动力学过程起作用，显示出双重作用。一方面，免疫系统可以激活一些免疫细胞来杀死肿瘤细胞（TC），如细胞毒性T淋巴细胞（CTL）和自然杀伤细胞（NK），但另一方面，更多的证据表明，一些免疫细胞可以帮助肿瘤逃逸，如调节性T细胞（TCLs）。本文提出了一个基于Tregs介导的肿瘤免疫逃逸机制的肿瘤免疫相互作用模型。当辅助性T细胞（Helper T cells，HTCs）对肿瘤抗原的刺激率低于临界值时，肿瘤和免疫共存平衡在其存在区域内始终稳定。当HTCs的刺激率高于临界值时，TdR对效应细胞（ECs）的抑制率会破坏共存平衡，引起Hopf分岔，产生极限环。该模型表明，TGFAP可能在触发肿瘤免疫逃逸中起关键作用。此外，我们还介绍了过继性细胞免疫疗法（ACI）和单克隆抗体免疫疗法（MAI）作为增强免疫系统对抗肿瘤的治疗方法。结果表明，ACI对TC的抑制作用更强，而MAI则能延迟TdR对EC的抑制作用。结果还表明，两种免疫疗法的组合可以控制TC，并且比单一免疫疗法可以控制的更好地降低TcR的抑制作用。
The immune system against tumors acts through a complex dynamical process showing a dual role. On the one hand, the immune system can activate some immune cells to kill tumor cells (TCs), such as cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs), but on the other hand, more evidence shows that some immune cells can help tumor escape, such as regulatory T cells (Tregs). In this paper, we propose a tumor immune interaction model based on Tregs-mediated tumor immune escape mechanism. When helper T cells’ (HTCs) stimulation rate by the presence of identified tumor antigens is below critical value, the coexistence (tumor and immune) equilibrium is always stable in its existence region. When HTCs stimulation rate is higher than the critical value, the inhibition rate of effector cells (ECs) by Tregs can destabilize the coexistence equilibrium and cause Hopf bifurcations and produce a limit cycle. This model shows that Tregs might play a crucial role in triggering the tumor immune escape. Furthermore, we introduce the adoptive cellular immunotherapy (ACI) and monoclonal antibody immunotherapy (MAI) as the treatment to boost the immune system to fight against tumors. The numerical results show that ACI can control TCs more, while MAI can delay the inhibitory effect of Tregs on ECs. The result also shows that the combination of both immunotherapies can control TCs and reduce the inhibitory effect of Tregs better than a single immunotherapy can control.