RIG‐I‐mediated innate immune signaling in tumors reduces the therapeutic effect of oncolytic vesicular stomatitis virus

Abstract

Abstract Background Oncolytic viral therapy is a promising method for tumor treatment. Currently, several oncolytic viruses (OVs) have been used as tumor therapy at different phases of research and clinical trials. OVs not only directly lyse tumor cells due to viral replication but also initiate host antitumor immune responses. Previous studies have primarily focused on how OVs activate adaptive immune responses in immune cells. However, the role of innate immune responses in tumors induced by OVs remains unclear. Methods To determine the innate immune responses induced by vesicular stomatitis virus (VSV), the mutant VSVΔM51 strain was used for the infection and quantitative polymerase chain reaction (qPCR) was employed to measure the transcriptional levels of antiviral genes. The knockdown efficiency of RIG‐I was examined by qPCR. Viral titers were measured by plaque assays. Tumor models were established by intradermally implanting RIG‐I‐knockdown and control LLC cells into the flank of wild type C57BL/6J mice. When the tumors reached approximately 50mm3, they were infected with VSVΔM51 via intratumoral injections to examine its therapeutic effect. Results Infection with VSVΔM51 triggered remarkable innate immune responses in several tumor cell lines through the cytoplasmic RIG‐I sensing pathway. Moreover, we found that intratumoral injection of VSVΔM51 effectively reduced tumor growth in murine LCC lung cancer model. Importantly, VSVΔM51‐induced antitumor therapy was more effective in murine LLC tumor model established using Rig‐I‐knockdown cells compared with the tumor model established using control cells. Conclusion RIG‐I‐mediated innate immune signaling in tumor cells plays a negative role in regulating antitumor therapy with VSVΔM51 virus.

Keywords

• cancer therapy
• innate immune
• oncolytic vesicular stomatitis virus
• RIG‐I