The role of cancer metabolism in defining the success of oncolytic viro-immunotherapy

• Published in: Cytokine & growth factor reviews Vol. 56; pp. 115 - 123
• Main Authors: Dyer, Arthur, Frost, Sally, Fisher, Kerry D., Seymour, Len W.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2020
• Subjects: Advanced Basic Science; Cancer metabolism; Cancer Vaccines; Humans; Immunotherapy; Metabolism; Neoplasms - therapy; Oncolytic Virotherapy; Oncolytic virus; Oncolytic Viruses - immunology; Oncolytic virotherapy; Oncolytic virus; Cancer metabolism; Metabolism; Immunotherapy
• ISSN: 1359-6101; 1879-0305
• DOI: 10.1016/j.cytogfr.2020.07.006

[Display omitted] •Each oncolytic virus type has essential nutrients required for optimal oncolysis.•In vitro work often uses conditions that do not reflect conditions within tumours in vivo.•Reducing nutrients can trigger the differential stress response leaving tumour cells vulnerable to treatment while protecting non-tumour cells.•Understanding the metabolic requirements of an oncolytic virus can permit improved treatment strategies. Oncolytic viruses infect, replicate in, and kill cancer cells selectively without harming normal cells. The rapidly expanding clinical development of oncolytic virotherapy is an exciting interdisciplinary field that provides insights into virology, oncology, and immunotherapy. Recent years have seen greater focus on rational design of cancer-selective viruses together with strategies to exploit their immunostimulatory capabilities, ultimately to develop powerful oncolytic cancer vaccines. However, despite great interest in the field, many important experiments are still conducted under optimum conditions in vitro, with many nutrients present in excess and with cellular stress kept to a minimum. Whilst this provides a convenient platform for cell culture, it bears little relation to the typical conditions found within a tumour in vivo, where cells are often subject to a range of metabolic and environmental stresses. Viral infection and cancer will both lead to production of metabolites that are also not present in media in vitro. Understanding how oncolytic viruses interact with cells exposed to more representative metabolic conditions in vitro represents an under-explored area of study that could provide valuable insight into the intelligent design of superior oncolytic viruses and help bridge the gap between bench and bedside. This review summarises the major metabolic pathways altered in cancer cells, during viral infection and highlights possible targets for future studies.