Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: a mathematical approach

Nada Almuallem, Dumitru Trucu, Raluca Eftimie (Lead / Corresponding author)

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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.
Original languageEnglish
Pages (from-to)764-799
Number of pages36
JournalMathematical Biosciences and Engineering
Volume18
Issue number1
Early online date18 Dec 2020
DOIs
Publication statusPublished - 2021

Keywords

  • Mathematical model
  • Vesicular Stomatitis Virus (VSV)
  • Breast cancer cells
  • M1 macrophages
  • M2 macrophages
  • Asymptotic dynamics

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