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Oncolytic virotherapy - the use of viruses that specifically kill tumor cells- is an innovative and highly promising route for treating cancer. However, itstherapeutic outcomes are mainly impaired by the host immune response to theviral infection. In the present work, we propose a multiscale mathematicalmodel to study how the immune response interferes with the viral oncolyticactivity. The model assumes that cytotoxic T cells can induce apoptosis ininfected cancer cells and that free viruses can be inactivated by neutralizingantibodies or cleared at a constant rate by the innate immune response. Oursimulations suggest that reprogramming the immune microenvironment in tumorscould substantially enhance the oncolytic virotherapy in immune-competenthosts. Viable routes to such reprogramming are either in situ virus-mediatedimpairing of CD$8^+$ T cells motility or blockade of B and T lymphocytesrecruitment. Our theoretical results can shed light on the design of viralvectors or new protocols with neat potential impacts on the clinical practice.

Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer