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In this study we investigate computationally tumour-oncolytic virus(OV)interactions that take place within a heterogeneous ExtraCellular Matrix (ECM).The ECM is viewed as a mixture of two constitutive phases, namely a fibre phaseand a non-fibre phase. The multiscale mathematical model presented here focuseson the nonlocal cell-cell and cell-ECM interactions, and how these interactionsmight be impacted by the infection of cancer cells with the OV. At macroscalewe track the kinetics of cancer cells, virus particles and the ECM. Atmicroscale we track (i) the degradation of ECM by matrix degrading enzymes(MDEs) produced by cancer cells, which further influences the movement oftumour boundary; (ii) the re-arrangement of the microfibres that influences there-arrangement of macrofibres (i.e., fibres at macroscale). With the help ofthis new multiscale model, we investigate two questions: (i) whether theinfected cancer cell fluxes are the result of local or non-local advection inresponse to ECM density; and (ii) what is the effect of ECM fibres on the thespatial spread of oncolytic viruses and the outcome of oncolytic virotherapy.

Nonlocal multiscale modelling of tumour-oncolytic viruses interactions within a heterogeneous fibrous/non-fibrous extracellular matrix