Rhodes2019 - Immune-Mediated theory of Metastasis

Model Identifier
BIOMD0000000926
Short description
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<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>
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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
Submitter of this revision: Ahmad Zyoud
Modellers: Szeyi Ng, Ahmad Zyoud
Metadata information
is (3 statements)
hasTaxon (1 statement)
hasProperty (5 statements)
isDescribedBy (1 statement)
BioModels Database
MODEL1910020003
BioModels Database MODEL1910020003
BioModels Database BIOMD0000000926
BioModels Database MODEL1910020003
BioModels Database BIOMD0000000926
hasTaxon (1 statement)
hasProperty (5 statements)
Experimental Factor Ontology
cancer
Mathematical Modelling Ontology Ordinary differential equation model
Gene Ontology immune response
NCIt Metastasis
NCIt Immune
Mathematical Modelling Ontology Ordinary differential equation model
Gene Ontology immune response
NCIt Metastasis
NCIt Immune
isDescribedBy (1 statement)
Curation status
Curated
Modelling approach(es)
Tags
Connected external resources
Name | Description | Size | Actions |
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Model files |
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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 |
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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
- Submitted on: Mar 28, 2020 7:36:07 AM
- Submitted by: Ahmad Zyoud
- With comment: Automatically added model identifier BIOMD0000000926
-
Version: 2
- 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
of this model will only be shown to the submitter and their collaborators.
Legends
: Variable used inside SBML models
: 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)
(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)