Resumen
Oncolytic viruses are emerging immunotherapeutics in cancer treatments. The conflicting role of innate immunity in the antitumor activity of oncolytic viruses is still a matter of debate. The STING-dependent DNA sensing axis is considered detrimental for viral replication and cancer cell clearance. Accordingly, we observed that STING loss in tumor cells was associated with improved lytic potential by a herpes-based oncolytic virus. However, STING-knockout cancer cells infected with the oncolytic virus showed impaired immunogenicity, as immunogenic cell death was improperly triggered. In agreement with these observations, STING-knockout tumors raised in a murine syngeneic model were more resistant to a combined treatment of the oncolytic virus with PD-1 blockade. The present study demonstrates the antitumor benefit of antiviral immunity and sheds lights on the mechanisms of immune resistance to oncovirotherapy exerted by STING-loss in tumor cells.