Rhodes2019 - Immune-Mediated theory of MetastasisNew Model

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Short description
Abstract: 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.
Format
SBML (L2V4)
Related Publication
  • A Mathematical Model for the Immune-Mediated Theory of Metastasis
  • Adam Rhodes, Thomas Hillen
  • Jornal of Theoretical Biology , 9/ 2019
  • 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 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.
Contributors
Szeyi Ng

Metadata information

hasProperty
Experimental Factor Ontology cancer
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Metastasis
Gene Ontology immune response
NCIt Immune
isDescribedBy

Curation status
Non-curated


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Model files

Rhodes2019-Immune-Mediated theory of Metastasis.xml SBML L2V4 file for the model 153.10 KB Preview | Download

Additional files

Rhodes2019-Immune-Mediated theory of Metastasis.cps COPASI 4.24 (Build 197) file for the model 199.21 KB Preview | Download

  • Model originally submitted by : Szeyi Ng
  • Submitted: 02-Oct-2019 14:00:44
  • Last Modified: 02-Oct-2019 14:00:44
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 02-Oct-2019 14:00:44
    • Submitted by: Szeyi Ng
    • With comment: Edited model metadata online.
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