Mathematical model creation for cancer chemo-immunotherapy
Mathematical model creation for cancer chemo-immunotherapy
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DOI：
10.1080/17486700802216301
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Preskill, Benjamin
中科院分区：
文献类型：
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作者：
de Pillis, Lisette;Fister, K. Renee;Preskill, Benjamin
在构建癌症治疗的数学模型中，最具挑战性的任务之一是从经验数据计算生物参数。如果一个模型涉及几个细胞群和治疗方式，这项任务变得越来越困难。一个由de Pillis等人构建的复杂模型，肿瘤的混合免疫疗法和化疗：建模，应用和生物学解释，J。238（2006），pp. 841-862;该疗法涉及肿瘤细胞、特异性和非特异性免疫细胞（自然杀伤（NK）细胞、CD 8 +T细胞和其他淋巴细胞），并采用化疗和两种免疫疗法（IL-2补充和CD 8 + T细胞输注）作为治疗方式。尽管上述模型总体上取得了成功，但说明IL-2对生长中的肿瘤的作用的问题仍然是开放的。在本文中，我们更新了de Pillis等人的模型，然后根据最近的经验数据仔细确定新模型参数的适当值。我们确定了新的NK和肿瘤抗原激活的CD 8 + T细胞计数平衡值;我们完成了IL-2动力学;我们修改了de Pillis等人的模型，以允许内源性IL-2产生，IL-2刺激的NK细胞增殖和IL-2依赖性CD 8 + T细胞自我调节。最后，我们表明免疫疗法对患者的潜在特异性疗效可能取决于实验可确定的参数。
One of the most challenging tasks in constructing a mathematical model of cancer treatment is the calculation of biological parameters from empirical data. This task becomes increasingly difficult if a model involves several cell populations and treatment modalities. A sophisticated model constructed by de Pillis et al., Mixed immunotherapy and chemotherapy of tumours: Modelling, applications and biological interpretations, J. Theor. Biol. 238 (2006), pp. 841-862; involves tumour cells, specific and non-specific immune cells (natural killer (NK) cells, CD8+T cells and other lymphocytes) and employs chemotherapy and two types of immunotherapy (IL-2 supplementation and CD8+T-cell infusion) as treatment modalities. Despite the overall success of the aforementioned model, the problem of illustrating the effects of IL-2 on a growing tumour remains open. In this paper, we update the model of de Pillis et al. and then carefully identify appropriate values for the parameters of the new model according to recent empirical data. We determine new NK and tumour antigen-activated CD8+T-cell count equilibrium values; we complete IL-2 dynamics; and we modify the model in de Pillis et al. to allow for endogenous IL-2 production, IL-2-stimulated NK cell proliferation and IL-2-dependent CD8+T-cell self-regulations. Finally, we show that the potential patient-specific efficacy of immunotherapy may be dependent on experimentally determinable parameters.