A mathematical model for the immune-mediated theory of metastasis

JOURNAL OF THEORETICAL BIOLOGY

卷:482

Article

Rhodes, Adam¹  Hillen, Thomas¹ 

[1] Univ Alberta, Dept Math & Stat Sci, CAB 632, Edmonton, AB T6G 2G1, Canada

关键词: Metastasis;    Ordinary differential equations;    Immune response;    Immunotherapies;    Metastatic cascade;   

DOI  :  10.1016/j.jtbi.2019.109999

来源: Elsevier

【 摘 要 】

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 proposed immune-mediated theory of metastasis, we develop a mathematical model for tumor-immune interactions at two anatomically distant sites, 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 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. (C) 2019 Elsevier Ltd. All rights reserved.

【 授权许可】

Free