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 infiltrating immune cells. In this theoretical study, we derive an ODE model to investigate interactions between breast cancer cells, virus (Vesicular Stomatitis Virus), and tumour-infiltrating macrophages with different phenotypes can impact dynamics viruses. complexity requires combined analytical-numerical approach understand transient asymptotic model. We use propose new biological hypotheses regarding elimination/relapse/persistence of: (i) macrophage polarisation/re-polarisation rates; (ii) infection rates cells virus; (iii) viral burst sizes for show that increasing rate at infects delay relapse even eliminate tumour. Increasing particles infect trigger transitions steady-state oscillatory dynamics, but it does not lead elimination unless is also very large. Moreover, confirm numerically tumour-induced M1$\to$M2 polarisation leads fast growth (if was reduced before by strong anti-tumour response). increase in viral-induced M2$\to$M1 re-polarisation reduces temporarily size, elimination. Finally, size more sensitive production viruses infected macrophages.