Rhodes2019 - Immune-Mediated theory of Metastasis

  public model
Model Identifier
BIOMD0000000926
Short description
<notes xmlns="http://www.sbml.org/sbml/level2/version4"> <body xmlns="http://www.w3.org/1999/xhtml"> <p>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.</p> </body> </notes>
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 , DOI: 10.1101/565531
  • 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
Submitter of the first revision: Szeyi Ng
Submitter of this revision: Ahmad Zyoud
Modellers: Szeyi Ng, Ahmad Zyoud

Metadata information

is (3 statements)
BioModels Database MODEL1910020003
BioModels Database MODEL1910020003
BioModels Database BIOMD0000000926

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (5 statements)
Experimental Factor Ontology cancer
Mathematical Modelling Ontology Ordinary differential equation model
Gene Ontology immune response
NCIt Metastasis
NCIt Immune

isDescribedBy (1 statement)
Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags
Immuno-oncology

Connected external resources

Name Description Size Actions

Model files
Rhodes2019-Immune-Mediated theory of Metastasis_V1.xml SBML L2V4 file Rhodes2019 - Immune-Mediated theory of MetastasisNew Model_Curated-Figure 3 181.88 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
Rhodes2019-Immune-Mediated theory of Metastasis.xml SBML L2V4 file Rhodes2019 - Immune-Mediated theory of MetastasisNew Model_Original 153.10 KB Preview | Download
Rhodes2019-Immune-Mediated theory of Metastasis_V1.cps COPASI version 4.27 (Build 217) Rhodes2019 - Immune-Mediated theory of MetastasisNew Model_Curated-Figure 3 220.29 KB Preview | Download
Rhodes2019-Immune-Mediated theory of Metastasis_V1.sedml sed-ml L1V2 Rhodes2019 - Immune-Mediated theory of MetastasisNew Model_Curated-Figure 3 6.27 KB Preview | Download

  • Model originally submitted by : Szeyi Ng
  • Submitted: Oct 2, 2019 2:00:44 PM
  • Last Modified: Mar 28, 2020 7:36:07 AM
Revisions
  • Version: 7 public model Download this version
    • Submitted on: Mar 28, 2020 7:36:07 AM
    • Submitted by: Ahmad Zyoud
    • With comment: Automatically added model identifier BIOMD0000000926
  • Version: 2 public model Download this version
    • Submitted on: Oct 2, 2019 2:00:44 PM
    • Submitted by: Szeyi Ng
    • With comment: Edited model metadata online.

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Tumor Cell u 1

cancer ; BTO:0006256 		1.0 mmol
Necrotic Cell v 2

C36123 ; C4968 		1.0E-16 mmol
TE immune Cell y 2

C4968 		1.0E-10 mmol
CT immune Cell x 1

C12543 ; cancer 		1694915.25423729 mmol
TE immune Cell y 1

cancer 		0.001 mmol
Tumor Cell u 2

BTO:0006256 ; C4968 		1.0E-12 mmol
Reactions
Reactions Rate Parameters
Tumor_Cell_u_1 => compartment*s_1*Tumor_Cell_u_1 s_1 = 0.01
Necrotic_Cell_v_2 => compartment*myu_2*Necrotic_Cell_v_2 myu_2 = 0.05
=> Tumor_Cell_u_1 compartment*gamma_1*g_1*Tumor_Cell_u_1 g_1 = 0.379999999285661; gamma_1 = 1.00000000000479
CT_immune_Cell_x_2 => TE_immune_Cell_y_2 compartment*ed_2*CT_immune_Cell_x_2 ed_2 = 5.0E-17
CT_immune_Cell_x_1 => TE_immune_Cell_y_1 compartment*ed_1*CT_immune_Cell_x_1 ed_1 = 5.0E-5
TE_immune_Cell_y_1 => compartment*tau_1*TE_immune_Cell_y_1 tau_1 = 0.05 1/d
=> TE_immune_Cell_y_1 compartment*f_1*TE_immune_Cell_y_1 f_1 = 2.49998437509766E-7
Tumor_Cell_u_2 => compartment*sigma_2*Tumor_Cell_u_2 sigma_2 = 0.299993171807403
=> CT_immune_Cell_x_1 compartment*alpha_1 alpha_1 = 1000000.0 1/d
Curator's comment:
(added: 28 Mar 2020, 07:35:32, updated: 28 Mar 2020, 07:35:32)
Figure 3C has been reproduced by Copasi 4.27 (Build 217)