Deciphering permissivity of human tumor ecosystems to oncolytic viruses

Area of Science:

• Oncology
• Immunology
• Virology

Background:

• Effective cancer therapy requires initiating a tumor-specific immune response.
• Oncolytic viruses (OV) are being investigated for their ability to trigger immunogenic cell death.
• Current preclinical models often fail to replicate the complexity of patient tumor ecosystems (TES), hindering clinical translation.

Purpose of the Study:

• To review the complex interplay between tumor ecosystems and oncolytic virus action.
• To discuss the impact of the tumor microenvironment (TME) on OV permissivity.
• To highlight the need for improved preclinical models for OV research.

Main Methods:

• Literature review focusing on oncolytic virotherapy and tumor microenvironment interactions.
• Analysis of recently developed preclinical human model systems.
• Discussion of factors influencing OV efficacy within the TES.

Main Results:

• The tumor microenvironment (TME) significantly influences oncolytic virus (OV) permissivity and efficacy.
• Existing preclinical models inadequately represent the human TES, leading to translation challenges.
• Understanding TES-OV interplay is crucial for developing effective oncolytic virotherapies.

Conclusions:

• There is an urgent need for advanced preclinical models that accurately mimic the human tumor ecosystem.
• The complex impact of the TME on OV action has been overlooked.
• Future research should focus on refining preclinical models to improve the clinical translation of oncolytic virus therapies.