Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer

Abstract

Oncolytic viral therapy is a new promising strategy against cancer. Oncolytic viruses (OVs) can replicate in cancer cells but not in normal cells, leading to lysis of the tumor mass. Beside this primary effect, OVs can also stimulate the immune system. Tumors are an immuno-suppressive environment in which the immune system is silenced in order to avoid the immune response against cancer cells. The delivery of OVs into the tumor wakes up the immune system so that it can facilitate a strong and durable response against the tumor itself. Both innate and adaptive immune responses contribute to this process, producing an immune response against tumor antigens and facilitating immunological memory. However, viruses are recognized by the immune system as pathogens and the consequent anti-viral response could represent a big hurdle for OVs. Finding a balance between anti-tumor and anti-viral immunity is, under this new light, a priority for researchers. In this review, we provide an overview of the various ways in which different components of the immune system can be allied with OVs. We have analyzed the different immune responses in order to highlight the new and promising perspectives leading to increased anti-tumor response and decreased immune reaction to the OVs.

Keywords: adenovirus; cancer-related inflammation; host immune response; immunotherapy; oncolytic virus; tumor immunity; vaccinia virus; virotherapy.

Figure 1

Anti-tumor immunity by oncolytic virus (OV) therapy: OVs can be modified in order to let them to replicate only in transformed cells. This process stimulates the immune system which is recruited into the tumor, skewing the neoplastic mass from an immuno-suppressive environment to an inflammatory site. Macrophages and T lymphocytes are key players in this process, producing cytokines that can recruit other immune cells and actively destroy cancer cells. This action generates an immunological memory that avoids cancer recurrence and synergizes with the oncolytic action of the viruses, potentially leading to tumor remission.