den Breems2015 - macrophage in cancer

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Model Identifier
BIOMD0000000759
Short description
The paper describes a model of re-polarisation of M2 and M1 macrophages and its role on cancer outcomes. Created by COPASI 4.25 (Build 207) This model is described in the article: The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes den Breems, Nicoline Y.; Eftimie, Raluca Journal of Theoretical Biology, 390, 23-39 Abstract: The anti-tumour and pro-tumour roles of Th1/Th2 immune cells and M1/M2 macrophages have been documented by numerous experimental studies. How- ever, it is still unknown how these immune cells interact with each other to control tumour dynamics. Here, we use a mathematical model for the inter- actions between mouse melanoma cells, Th2/Th1 cells and M2/M1 macro- phages, to investigate the unknown role of the re-polarisation between M1 and M2 macrophages on tumour growth. The results show that tumour growth is associated with a type-II immune response described by large num- bers of Th2 and M2 cells. Moreover, we show that: (i) the ratio k of the transition rates k12 (for the re-polarisation M1→M2) and k21 (for the re- polarisation M2→M1) is important in reducing tumour population, and (ii) the particular values of these transition rates control the delay in tumour growth and the final tumour size. We also perform a sensitivity analysis to investigate the effect of various model parameters on changes in the tumour cell population, and confirm that the ratio k alone and the ratio of M2 and M1 macrophage populations at earlier times (e.g., day 7), cannot always predict the final tumour size. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.
Format
SBML
Related Publication
  • The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes.
  • den Breems NY, Eftimie R
  • Journal of theoretical biology , 2/ 2016 , Volume 390 , pages: 23-39 , PubMed ID: 26551154
  • Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Lincoln 7476, New Zealand; Division of Mathematics, University of Dundee, Dundee DD1 4HN, United Kingdom; Division of Cancer Research, University of Dundee, Dundee DD1 9SY, United Kingdom. Electronic address: nicoline.vanloenen@lincolnuni.ac.nz.
  • The anti-tumour and pro-tumour roles of Th1/Th2 immune cells and M1/M2 macrophages have been documented by numerous experimental studies. However, it is still unknown how these immune cells interact with each other to control tumour dynamics. Here, we use a mathematical model for the interactions between mouse melanoma cells, Th2/Th1 cells and M2/M1 macrophages, to investigate the unknown role of the re-polarisation between M1 and M2 macrophages on tumour growth. The results show that tumour growth is associated with a type-II immune response described by large numbers of Th2 and M2 cells. Moreover, we show that (i) the ratio k of the transition rates k12 (for the re-polarisation M1→M2) and k21 (for the re-polarisation M2→M1) is important in reducing tumour population, and (ii) the particular values of these transition rates control the delay in tumour growth and the final tumour size. We also perform a sensitivity analysis to investigate the effect of various model parameters on changes in the tumour cell population, and confirm that the ratio k alone and the ratio of M2 and M1 macrophage populations at earlier times (e.g., day 7) cannot always predict the final tumour size.
Contributors
Submitter of the first revision: Jinghao Men
Submitter of this revision: Kausthubh Ramachandran
Modellers: Jinghao Men, Kausthubh Ramachandran

Metadata information

is (2 statements)
BioModels Database BIOMD0000000759
BioModels Database MODEL1907240004

isDescribedBy (1 statement)
PubMed 26551154

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (2 statements)
Gene Ontology immune response to tumor cell
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Non-curated
Modelling approach(es)
ordinary differential equation model
Tags
Immuno-oncology

Connected external resources

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Model files
denBreems2015.xml SBML L2V5 representation of the macrophage transition in cancer model 109.12 KB Preview | Download

Additional files
den Breems2015.omex COMBINE archive of the macrophage transition in cancer model 17.69 KB Preview | Download
denBreems2015.cps COPASI 4.29 (Build 228) representation of the macrophage transition in cancer model 137.15 KB Preview | Download
denBreems2015.sedml SED-ML representation of the macrophage transition in cancer model 5.05 KB Preview | Download

  • Model originally submitted by : Jinghao Men
  • Submitted: Jul 24, 2019 4:52:23 PM
  • Last Modified: Mar 5, 2021 11:50:59 AM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Mar 5, 2021 11:50:59 AM
    • Submitted by: Kausthubh Ramachandran
    • With comment: Updated model files - COPASI, SBML L2V5, SED-ML and COMBINE archive. Only SBML L3V1 and SED-ML files were previously available.
  • Version: 3 public model Download this version
    • Submitted on: Jul 24, 2019 4:52:23 PM
    • Submitted by: Jinghao Men
    • With comment: Automatically added model identifier BIOMD0000000759

(*) 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
M1

M1 Macrophage 		100.0 mmol
Ts

malignant cell 		1000000.0 mmol
Tn

malignant cell 		1000.0 mmol
M2

M2 Macrophage 		100.0 mmol
Th1

T-helper 1 cell 		0.0 mmol
Reactions
Reactions Rate Parameters
=> M1; Ts, Th1, M2 tumor_microenvironment*(as*Ts+am1*Th1)*M1*(1-(M1+M2)/bm) as = 1.0E-6 1/d; am1 = 5.0E-8 1/d; bm = 100000.0 1
M1 => tumor_microenvironment*dm1*M1 dm1 = 0.2 1/d
M2 => M1 tumor_microenvironment*k21*M2*M1 k21 = 4.0E-5 1/d
Ts => ; M1 tumor_microenvironment*dms*M1*Ts dms = 2.0E-6 1/d
Ts => ; Th1 tumor_microenvironment*dts*Th1*Ts dts = 5.3E-8 1/d
=> Tn; Ts tumor_microenvironment*r*Tn*(1-(Tn+Ts)/bt) r = 0.565 1/d; bt = 2.0E9 1
=> M2; Tn, Th2, M1 tumor_microenvironment*(an*Tn+am2*Th2)*M2*(1-(M2+M1)/bm) an = 5.0E-8 1/d; bm = 100000.0 1; am2 = 5.0E-8 1/d
Tn => ; M1 tumor_microenvironment*dmn*M1*Tn dmn = 2.0E-6 1/d
M1 => M2 tumor_microenvironment*k12*M1*M2 k12 = 5.0E-5 1/d
=> Th1; M1, Th2 tumor_microenvironment*rh1*M1*Th1*(1-(Th1+Th2)/bth) rh1 = 9.0E-6 1/d; bth = 1.0E8 1
Curator's comment:
(added: 24 Jul 2019, 16:51:53, updated: 24 Jul 2019, 16:51:53)
Publication figure 2 reproduced as per literature. Figure data is generated using COPASI 4.25 (build 197).