Mathematical Modeling of the Immune-Mediated Theory of Metastasis

Adam Rhodes (May 6, 2020)

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Abstract

Authors:
Adam Rhodes, Department of Mathematical and Statistical Science, University of Alberta
Prof. Thomas Hillen, Department of Mathematical and Statistical Science, University of Alberta

Accumulating experimental and clinical evidence suggest that the immune response to cancer is not exclusively anti-tumor. Indeed, the pro-tumor roles of the immune system — as suppliers of growth and pro-angiogenic factors or defenses against cytotoxic immune attacks, for example — have been long appreciated, but relatively few theoretical works have considered their effects. Inspired by the recently roposed “immune-mediated� theory of metastasis, we develop a mathematical model for tumor-immune interactions in the metastatic setting, which includes both anti- and pro-tumor immune effects, and the experimentally observed tumor-induced phenotypic plasticity of immune cells (tumor “education� of the immune cells). Upon confrontation of our model to experimental data, we use it to evaluate the implications of the immune-mediated theory of metastasis. We find that tumor education of immune cells may explain the relatively poor performance of immunotherapies, and that many metastatic phenomena, including metastatic blow-up, dormancy, and metastasis to sites of injury, can also be explained by the immune-mediated theory of metastasis. Our results suggest that further work is warranted to fully elucidate the pro-tumor effects of the immune system in metastatic cancer.