Cancer cells infected with reoviruses produce signalling proteins that can result in the death of cancer cells even when isolated, finds a study in Molecular Cancer.

Reoviruses are dsRNA viruses that lack an outer envelope. Although highly prevalent among people and known to be present in the respiratory and enteric tracts, reoviruses only produce mild or subclinical symptoms. Normal cells, it is now known, are protected from reovirus infection by a protein called PKR, but in cancerous cells, a cellular signalling protein Ras, is produced that blocks PKR activity.  Recent interest has focused on the use of reoviruses as oncology agents due to their ability to infect and induce death in a range of human malignancies while sparing normal cells.

Previous studies have shown that reoviruses can induces apoptotic death in human melanoma cells, and further more that death is associated with secretion of inflammatory chemokines/cytokines. Human melanoma cells lines undergo reovirus induced apoptotic death, with death found to be accompanied by the release of inflammatory chemokines and cytokines.

In the current study, Alan Melcher and colleagues from St James’s University Hospital (Leeds, UK) investigated whether a wider panel of chemokines and cytokines were induced when cancer cells were infected by reoviruses.  For the study, the investigators compared growth medium taken from melanoma cell lines infected with reoviruses or left untreated.

Medium taken from the melanoma cells infected with reoviruses, they found, contained a range of small pro-inflammatory proteins including an interleukin (IL-8), Type 1 Interferon (INF-β), eotaxin and IP-10. Furthermore the team were able to show that the proteins recruited   Natural Killer cells, dendritic cells and anti melanoma cytotoxic T cells in the absence of the reoviruses.

 “Bystander immune-mediated therapy may well be an important component in the treatment of cancer by reoviruses, and may have potential in treating cancer even in the absence of live virus,” suggests Melcher.

Reference

L Steele, F Errington, R Prestwich, et al. Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-кB mediated and supports innate and adaptive anti-tumour immune priming. Molecular Cancer doi : 10.1186/1476-4598-10-20