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Updated: Jan 18, 2026

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

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IRF7 drives resistance to oncolytic virotherapy by restricting viral replication and suppressing antitumor immunity

Jie Wang1, Dongping Zhang1, Yi Yang1

  • 1State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China.

Biochemical and Biophysical Research Communications
|September 9, 2025
PubMed

Insights

Interferon regulatory factor 7 (IRF7) drives resistance to oncolytic virus (OV) cancer therapy. Targeting IRF7 can improve OV efficacy by enhancing anti-tumor immunity.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunotherapy
  • Molecular mechanisms of cancer resistance

Background:

  • Oncolytic viruses (OVs) show promise for cancer immunotherapy through tumor lysis and immune stimulation.
  • Tumor-intrinsic resistance significantly limits the effectiveness of OV therapy.
  • Identifying resistance mechanisms is crucial for improving OV-based cancer treatments.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying resistance to oncolytic viruses in colon cancer.
  • To identify key regulators involved in OV resistance.
  • To evaluate the therapeutic potential of targeting identified resistance factors.

Main Methods:

  • Establishment of an OV-resistant MC38 colon cancer model (MC38OVR).
  • Analysis of interferon regulatory factor 7 (IRF7) expression in resistant cells.
  • In vitro assessment of viral infection, replication, and cytotoxicity following IRF7 knockdown.
  • In vivo evaluation of OV efficacy in immunocompetent versus immunodeficient mice.
  • Flow cytometry analysis of immune cell markers (CD80, CD86, PD-L1) and T cell infiltration.

Main Results:

  • Interferon regulatory factor 7 (IRF7) was significantly upregulated in OV-resistant MC38OVR cells.
  • IRF7 knockdown enhanced OV infection, replication, and tumor cell killing in vitro.
  • OV efficacy was markedly reduced in immunodeficient NOD mice compared to immunocompetent mice, highlighting the role of adaptive immunity.
  • IRF7 knockdown modulated tumor cell surface markers (increased CD80/CD86, decreased PD-L1), promoting T cell infiltration and activation.

Conclusions:

  • Interferon regulatory factor 7 (IRF7) is a critical mediator of intrinsic resistance to oncolytic viruses in colon cancer.
  • Targeting IRF7 can overcome OV resistance by enhancing viral activity and promoting anti-tumor adaptive immunity.
  • IRF7 represents a promising therapeutic target to improve the efficacy of oncolytic viroimmunotherapy.
Keywords:
Cancer immunotherapyIRF7Interferon signalingOncolytic virusesResistanceTumor microenvironment

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