Tumor Control by Cytomegalovirus: A Door Open for Oncolytic Virotherapy?

Belonging to the herpesviridae family, human cytomegalovirus (HCMV) is a well-known ubiquitous pathogen that establishes a lifelong infection in humans. Recently, a beneficial tumor-cytoreductive role of CMV infection has been defined in human and animal models. Described as a potential anti-tumoral activity, HCMV modulates the tumor microenvironment mainly by inducing cell death through apoptosis and prompting a robust stimulatory effect on the immune cells infiltrating the tumor tissue. However, major current limitations embrace transient protective effect and a viral dissemination potential in immunosuppressed hosts. The latter could be counteracted through direct viral intratumoral delivery, use of non-human strains, or even defective CMV vectors to ascertain transformed cells-selective tropism. This potential oncolytic activity could be complemented by tackling further platforms, namely combination with immune checkpoint inhibitors or epigenetic therapy, as well as the use of second-generation chimeric oncovirus, for instance HCMV/HSV-1 oncolytic virus. Overall, preliminary data support the use of CMV in viral oncolytic therapy as a viable option, establishing thus a potential new modality, where further assessment through extensive basic research armed by molecular biotechnology is compulsory.