title: Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer.
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 this paper, 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 CD8(+) 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.
authors.affiliation: Departamento de Física, Universidade Federal de Viçosa, 36570-000 Viçosa, MG, Brazil.
authors.forename: Leticia R
authors.initials: LR
authors.lastname: Paiva
authors.forename: Hallan S
authors.initials: HS
authors.lastname: Silva
authors.forename: Silvio C
authors.initials: SC
authors.lastname: Ferreira
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Martins
mesh_terms: D056704:Adaptive Immunity; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003198:Computer Simulation; D006801:Humans; D007113:Immunity, Innate; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000276:immunology*