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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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IFNAR blockade synergizes with oncolytic VSV to prevent virus-mediated PD-L1 expression and promote antitumor T cell

Nader El-Sayes1,2, Scott Walsh1, Alyssa Vito1,2

  • 1Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.

Molecular Therapy Oncolytics
|April 11, 2022
PubMed

Insights

Oncolytic virotherapy can be improved by blocking type I interferon (IFN-I) signaling. This approach reduces immunosuppression, enhances T cell responses, and boosts therapeutic efficacy against tumors.

Area of Science:

  • Immunology
  • Oncology
  • Virology

Background:

  • Oncolytic virotherapies leverage antitumor immunity but the role of type I interferon (IFN-I) remains unclear.
  • Emerging evidence suggests IFN-I may have immunosuppressive effects in cancer therapies.
  • Understanding IFN-I's impact is crucial for optimizing oncolytic virotherapy efficacy.

Purpose of the Study:

  • To investigate the role of oncolytic virus-induced IFN-I in modulating antitumor immunity.
  • To determine if inhibiting IFN-I signaling can enhance the effectiveness of oncolytic virotherapy.
  • To explore combination strategies involving IFN-I blockade and oncolytic virotherapy.

Main Methods:

  • Oncolytic virus administration in preclinical cancer models.
  • Assessment of PD-L1 expression on tumor cells and leukocytes.
  • Intervention with a monoclonal antibody targeting the IFN-I receptor (IFNAR).
  • Evaluation of tumor-specific T cell responses and therapeutic outcomes.

Main Results:

  • Oncolytic virus-induced IFN-I upregulated PD-L1 expression in a IFNAR-dependent manner.
  • IFNAR blockade reduced IFN-I-induced PD-L1 expression and enhanced T cell effector functions.
  • Combining IFNAR blockade with oncolytic virotherapy improved therapeutic response, comparable to PD-L1 blockade.

Conclusions:

  • Type I interferon plays a critical immunosuppressive role in oncolytic virotherapy.
  • Inhibiting IFN-I signaling is a viable strategy to overcome treatment resistance.
  • Combination therapy of IFNAR blockade and oncolytic virotherapy shows significant promise for cancer treatment.
Keywords:
IFNIFNARPD-L1immune checkpointimmunotherapyoncolytic virus

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