Metastatic seeding of distant organs can occur in the very early stages of primary tumor development. Once seeded, these micrometastases may enter a dormant phase that can last decades. Curiously, the surgical removal of the primary tumor can stimulate the accelerated growth of distant metastases, a phenomenon known as metastatic blow-up. Recent clinical evidence has shown that the immune response can have strong tumor promoting effects. In this work, we investigate if the pro-tumor effects of the immune response can have a significant contribution to metastatic dormancy and metastatic blow-up. We develop an ordinary differential equation model of the immune-mediated theory of metastasis. We include both anti- and pro-tumor immune effects, in addition to the experimentally observed phenomenon of tumor-induced immune cell phenotypic plasticity. Using geometric singular perturbation analysis, we derive a rather simple model that captures the main processes and, at the same time, can be fully analyzed. Literature-derived parameter estimates are obtained, and model robustness is demonstrated through a time dependent sensitivity analysis. We determine conditions under which the parameterized model can successfully explain both metastatic dormancy and blow-up. The results confirm the significant active role of the immune system in the metastatic process. Numerical simulations suggest a novel measure to predict the occurrence of future metastatic blow-up in addition to new potential avenues for treatment of clinically undetectable micrometastases.

远处器官的转移性播种可发生在原发性肿瘤发展的早期。一旦播种，这些微转移可能会进入可能持续数十年的休眠期。奇怪的是，手术切除原发肿瘤可以刺激远处转移的加速生长，这种现象被称为转移性爆炸。最近的临床证据表明，免疫反应可以具有很强的促肿瘤作用。在这项工作中，我们调查了免疫应答的促肿瘤作用是否对转移性休眠和转移性爆炸有重大贡献。我们开发了免疫介导的转移理论的常微分方程模型。除了实验观察到的肿瘤诱导的免疫细胞表型可塑性现象外，我们还包括抗肿瘤和促肿瘤免疫作用。使用几何奇异摄动分析，我们得出了一个相当简单的模型，该模型捕获了主要过程，同时可以进行全面分析。获得了文献衍生的参数估计值，并通过时变敏感性分析证明了模型的鲁棒性。我们确定参数化模型可以成功解释转移性休眠和爆炸的条件。结果证实了免疫系统在转移过程中的重要主动作用。