Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review)

Area of Science:

• Oncolytic virotherapy
• Cancer immunotherapy
• Tumor microenvironment

Background:

• Oncolytic viruses (OV) are engineered to target and destroy cancer cells, offering a novel immunotherapy approach.
• Despite their potential, clinical efficacy of OV has been limited by various resistance mechanisms.
• Understanding these resistance factors is crucial for enhancing OV therapeutic outcomes.

Purpose of the Study:

• To comprehensively review the multifaceted mechanisms of resistance to oncolytic virus therapy.
• To identify key factors within tumors, stromal cells, the extracellular matrix (ECM), and host immunity that impede OV effectiveness.
• To propose potential strategies for overcoming OV resistance and improving treatment efficacy.

Main Methods:

• Literature review synthesizing current evidence on OV resistance mechanisms.
• Analysis of tumor cell characteristics, stromal and ECM interactions, and host immune responses.
• Identification of potential therapeutic interventions and biomarkers.

Main Results:

• Tumor heterogeneity, lack of specific viral tropism, and off-target effects contribute to resistance.
• Extracellular matrix components, such as hyaluronic acid, can hinder viral delivery and penetration.
• Host immune responses, including premature viral clearance, significantly impact OV efficacy.
• Tumor cell characteristics, stromal factors, and immune status are interconnected dimensions of OV resistance.

Conclusions:

• Overcoming OV resistance requires a multi-pronged approach addressing tumor, stromal, and immune factors.
• Strategies such as identifying predictive biomarkers, using ECM-degrading enzymes, and combining OV with immune checkpoint inhibitors show promise.
• Optimizing OV therapy holds potential for improved immunotherapeutic outcomes in cancer patients.