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Abstract
One of the cancer hallmarks is immune evasion mediated by the tumour microenvironment (TME). Oncolytic virotherapy is a form of immunotherapy based on the application of oncolytic viruses (OVs) that selectively replicate in and induce the death of tumour cells. Virotherapy confers reciprocal interaction with the host’s immune system. The aim of this review is to explore the role of macrophage-mediated responses in oncolytic virotherapy efficacy. The approach was to study current scientific literature in this field in order to give a comprehensive overview of the interactions of OVs and macrophages and their effects on the TME. The innate immune system has a central influence on the TME; tumour-associated macrophages (TAMs) generally have immunosuppressive, tumour-supportive properties. In the context of oncolytic virotherapy, macrophages were initially thought to predominantly contribute to anti-viral responses, impeding viral spread. However, macrophages have now also been found to mediate transport of OV particles and, after TME infiltration, to be subjected to a phenotypic shift that renders them pro-inflammatory and tumour-suppressive. These TAMs can present tumour antigens leading to a systemic, durable, adaptive anti-tumour immune response. After phagocytosis, they can recirculate carrying tissue-derived proteins, which potentially enables the monitoring of OV replication in the TME. Their role in therapeutic efficacy is therefore multifaceted, but based on research applying relevant, immunocompetent tumour models, macrophages are considered to have a central function in anti-cancer activity. These novel insights hold important clinical implications. When optimised, oncolytic virotherapy, mediating multifactorial inhibition of cancer immune evasion, could contribute to improved patient survival.
Highlights
Increasing research into the role of the immune system in tumour formation and progression has revealed immune cell evasion to be a central cancer hallmark [1]
Oncolytic virotherapy is a form of immunotherapy and refers to the administration of viruses that conditionally replicate in tumour cells and activate the immune system [2]
These activated cells affect the lysis of oncolytic viruses (OVs)-infected cancer cells as well as provide a link to adaptive immune cells that are recruited by the inflammatory tumour microenvironment (TME) and that react against virus-specific antigens [54]
Summary
Increasing research into the role of the immune system in tumour formation and progression has revealed immune cell evasion to be a central cancer hallmark [1]. This has led to the development of cancer immunotherapies designed to counteract the immunosuppressive characteristics of the tumour microenvironment (TME) and to target tumour antigens. Other cells in the TME subsequently acquire evasive immune programmes These heterologous cell types can actively affect the clinical response to treatments, constituting an important determinant in therapeutic outcome [7]
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