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Updated: Aug 19, 2025
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
RIG-I-mediated innate immune signaling in tumors reduces the therapeutic effect of oncolytic vesicular stomatitis
Pengfei Zhang1,2,3, Xinyu Han2,3, Weiqi Tan2,3
1School of Life Sciences, Anhui Agricultural University, Hefei, China.
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.
Insights
Oncolytic virus therapy using vesicular stomatitis virus (VSVΔM51) shows promise for tumor treatment. However, RIG-I innate immune signaling in tumor cells negatively impacts VSVΔM51-mediated antitumor effects.
Area of Science:
- Oncolytic virology
- Immunology
- Cancer research
Background:
- Oncolytic viruses (OVs) offer a dual mechanism for tumor treatment: direct lysis and immune stimulation.
- While adaptive immune responses to OVs are well-studied, the role of innate immunity within tumors remains largely unexplored.
Purpose of the Study:
- To investigate the role of innate immune responses, specifically RIG-I signaling, in oncolytic viral therapy using vesicular stomatitis virus (VSV).
- To evaluate the therapeutic efficacy of VSVΔM51 in a murine lung cancer model and assess the impact of RIG-I knockdown on treatment outcomes.
Main Methods:
- Utilized a mutant strain of vesicular stomatitis virus (VSVΔM51) for oncolytic viral therapy studies.
- Quantified antiviral gene expression via quantitative polymerase chain reaction (qPCR) and measured viral titers using plaque assays.
- Established LLC tumor models in C57BL/6J mice, including those with RIG-I knockdown, and assessed therapeutic effects of intratumoral VSVΔM51 injection.
Main Results:
- VSVΔM51 infection activated innate immune responses in tumor cells via the RIG-I sensing pathway.
- Intratumoral VSVΔM51 injection significantly inhibited tumor growth in a murine LLC lung cancer model.
- Antitumor therapy mediated by VSVΔM51 was more effective in tumors with RIG-I knockdown compared to control tumors.
Conclusions:
- RIG-I-mediated innate immune signaling within tumor cells plays a suppressive role in the efficacy of VSVΔM51 oncolytic viral therapy.
- Targeting or modulating RIG-I signaling could potentially enhance the effectiveness of oncolytic virotherapy.
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