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

TL;DR

This paper develops a multiscale mathematical model to understand how immune responses hinder oncolytic virus therapy in cancer, suggesting immune microenvironment reprogramming could improve treatment outcomes.

Contribution

It introduces a novel multiscale model analyzing immune effects on viral cancer therapy and proposes strategies to enhance efficacy by immune microenvironment modulation.

Findings

Reprogramming immune microenvironment enhances viral therapy efficacy.

In situ virus-mediated impairment of CD8+ T cells improves outcomes.

Blocking lymphocyte recruitment can boost oncolytic virotherapy.

Abstract

Oncolytic virotherapy - the use of viruses that specifically kill tumor cells - is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In the present work, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD$8^+$ T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.