Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach
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 Vi...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
AIMS Press
2021-04-01
|
| Series: | Mathematical Biosciences and Engineering |
| Subjects: | |
| Online Access: | http://www.aimspress.com/article/doi/10.3934/mbe.2021041?viewType=HTML |
| _version_ | 1818441151815876608 |
|---|---|
| author | Nada Almuallem Dumitru Trucu Raluca Eftimie |
| author_facet | Nada Almuallem Dumitru Trucu Raluca Eftimie |
| author_sort | Nada Almuallem |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T18:23:42Z |
| format | Article |
| id | doaj.art-7a7f3141232f4a3caa8aada6b9e5e8e1 |
| institution | Directory Open Access Journal |
| issn | 1551-0018 |
| language | English |
| last_indexed | 2024-12-14T18:23:42Z |
| publishDate | 2021-04-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | Mathematical Biosciences and Engineering |
| spelling | doaj.art-7a7f3141232f4a3caa8aada6b9e5e8e12022-12-21T22:51:58ZengAIMS PressMathematical Biosciences and Engineering1551-00182021-04-0118176479910.3934/mbe.2021041Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approachNada Almuallem0Dumitru Trucu1Raluca Eftimie2Department of Mathematics, University of Dundee, Dundee, DD1 4HN, UKDepartment of Mathematics, University of Dundee, Dundee, DD1 4HN, UKDepartment of Mathematics, University of Dundee, Dundee, DD1 4HN, UKThe 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.http://www.aimspress.com/article/doi/10.3934/mbe.2021041?viewType=HTMLmathematical modelvesicular stomatitis virus (vsv)breast cancer cellsm1 macrophagesm2 macrophagesasymptotic dynamics |
| spellingShingle | 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 mathematical model vesicular stomatitis virus (vsv) breast cancer cells m1 macrophages m2 macrophages asymptotic dynamics |
| title | Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach |
| title_full | Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach |
| title_fullStr | Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach |
| title_full_unstemmed | Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach |
| title_short | Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach |
| title_sort | oncolytic viral therapies and the delicate balance between virus macrophage tumour interactions a mathematical approach |
| topic | mathematical model vesicular stomatitis virus (vsv) breast cancer cells m1 macrophages m2 macrophages asymptotic dynamics |
| url | http://www.aimspress.com/article/doi/10.3934/mbe.2021041?viewType=HTML |
| work_keys_str_mv | AT nadaalmuallem oncolyticviraltherapiesandthedelicatebalancebetweenvirusmacrophagetumourinteractionsamathematicalapproach AT dumitrutrucu oncolyticviraltherapiesandthedelicatebalancebetweenvirusmacrophagetumourinteractionsamathematicalapproach AT ralucaeftimie oncolyticviraltherapiesandthedelicatebalancebetweenvirusmacrophagetumourinteractionsamathematicalapproach |