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Den Breems2015 - macrophage in cancer

ABSTRACT: 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.

SUBMITTER: Jinghao Men

PROVIDER: BIOMD0000000759 | BioModels | 2021-03-05

REPOSITORIES: BioModels

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The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes.

den Breems Nicoline Y NY Eftimie Raluca R

Journal of theoretical biology 20151110

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 gro ...[more]

PMID: 26551154

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Project description:The paper describes a model of interaction of Th cells and macrophage in melanoma. Created by COPASI 4.25 (Build 207) This model is described in the article: Modelling and investigation of the CD4 T cells – Macrophages paradox in melanoma immunotherapies Raluca Eftimie, Haneen Hamam Journal of Theoretical Biology 420 (2017) 82–104 Abstract: It is generally accepted that tumour cells can be eliminated by M1 anti-tumour macrophages and CD8+ T cells. However, experimental results over the past 10–15 years have shown that B16 mouse melanoma cells can be eliminated by the CD4+ T cells alone (either Th1 or Th2 sub-types), in the absence of CD8+ T cells. In some studies, elimination of B16 melanoma was associated with a Th1 immune response (i.e., elimination occurred in the presence of cytokines produced by Th1 cells), while in other studies melanoma elimination was associated with a Th2 immune response (i.e., elimination occurred in the presence of cytokines produced by Th2 cells). Moreover, macrophages have been shown to be present inside the tumours, during both Th1 and Th2 immune responses. To investigate the possible biological mechanisms behind these apparently contradictory results, we develop a class of mathematical models for the dynamics of Th1 and Th2 cells, and M1 and M2 macrophages in the presence/absence of tumour cells. Using this mathematical model, we show that depending on the re- polarisation rates between M1 and M2 macrophages, we obtain tumour elimination in the presence of a type-I immune response (i.e., more Th1 and M1 cells, compared to the Th2 and M2 cells), or in the presence of a type- II immune response (i.e., more Th2 and M2 cells). Moreover, tumour elimination is also possible in the presence of a mixed type-I/type-II immune response. Tumour growth always occurs in the presence of a type-II immune response, as observed experimentally. Finally, tumour dormancy is the result of a delicate balance between the pro-tumour effects of M2 cells and the anti-tumour effects of M1 and Th1 cells. 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.

Project description:This mathematical model of the role of the innate immune responses generated by macrophages in the context of anti-tumour oncolytic viral therapies is described in the publication: Nada Almuallem, Dumitru Trucu, Raluca Eftimie. "Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach". Mathematical Biosciences and Engineering, 2021, 18(1): 764-799. doi: 10.3934/mbe.2021041 Comment: This model is represented by Equations 2.1a-f of the publication manuscript. Abstract: The success of oncolytic virotherapies depends on the tumour microenvironment, which contains a large number of infiltrating immune cells. In this theoretical study, we derive an ODE model to investigate the interactions between breast cancer tumour cells, an oncolytic virus (Vesicular Stomatitis Virus), and tumour-infiltrating macrophages with different phenotypes which can impact the dynamics of oncolytic viruses. The complexity of the model requires a combined analytical-numerical approach to understand the transient and asymptotic dynamics of this model. We use this model to propose new biological hypotheses regarding the impact on tumour elimination/relapse/persistence of: (i) different macrophage polarisation/re-polarisation rates; (ii) different infection rates of macrophages and tumour cells with the oncolytic virus; (iii) different viral burst sizes for macrophages and tumour cells. We show that increasing the rate at which the oncolytic virus infects the tumour cells can delay tumour relapse and even eliminate tumour. Increasing the rate at which the oncolytic virus particles infect the macrophages can trigger transitions between steady-state dynamics and oscillatory dynamics, but it does not lead to tumour elimination unless the tumour infection rate is also very large. Moreover, we confirm numerically that a large tumour-induced M1→M2 polarisation leads to fast tumour growth and fast relapse (if the tumour was reduced before by a strong anti-tumour immune and viral response). The increase in viral-induced M2→M1 re-polarisation reduces temporarily the tumour size, but does not lead to tumour elimination. Finally, we show numerically that the tumour size is more sensitive to the production of viruses by the infected macrophages.

Dataset Information

Den Breems2015 - macrophage in cancer

Publications

The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes.

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