The implications of oncolytic viruses targeting fibroblasts in enhancing the antitumoural immune response

Area of Science:

• Oncology
• Immunotherapy
• Virology

Background:

• Oncolytic viruses (OVs) are an emerging immunotherapy that selectively kill tumor cells, enhancing anti-tumor immunity.
• Limited efficacy of oncolytic virotherapy in solid tumors is attributed to immunosuppressive cancer-associated fibroblasts (CAFs).
• Recent strategies explore targeting CAFs with OVs to boost anti-tumor immune responses.

Purpose of the Study:

• To critically evaluate the experimental designs of OV therapies targeting CAFs.
• To identify limitations in current approaches for clinical translation.
• To propose improvements for enhancing OV efficacy in solid tumors.

Main Methods:

• Review of existing studies on OV and CAF interactions.
• Analysis of experimental methodologies, including animal models and targeting strategies.
• Consideration of transcriptomics for precise CAF targeting.

Main Results:

• Current OV strategies targeting CAFs often lack specificity, ignoring CAF heterogeneity and the presence of anti-tumor CAFs.
• Preclinical studies predominantly use murine models that do not fully replicate human tumor microenvironments.
• Lack of pre-clinical complete remission indicates a need for enhanced immunotherapeutic approaches.

Conclusions:

• Targeting CAFs with OVs requires greater specificity, potentially guided by transcriptomics, to avoid off-target effects.
• Future research should utilize humanized patient-derived xenograft models and primary human tumor biopsies for improved translational relevance.
• Enhancing anti-tumor immune responses is crucial for achieving complete remission with OV therapy.