Oncolytic virotherapy against the tumor microenvironment and its potential in pancreatic cancer

Area of Science:

• Oncology
• Virology
• Immunology

Background:

• The tumor microenvironment (TME) significantly influences tumor progression, angiogenesis, metastasis, and immune evasion.
• Oncolytic viruses (OVs) are emerging as a therapeutic strategy targeting both cancer cells and the TME.
• Pancreatic cancer is characterized by a dense desmoplastic stroma, hypovascularity, and profound immunosuppression, making TME-targeted therapies crucial.

Purpose of the Study:

• To review the mechanisms by which oncolytic viruses (OVs) can manipulate the tumor microenvironment (TME).
• To summarize the evidence supporting the application of TME-targeted OVs in pancreatic cancer therapy.
• To highlight strategies for using OVs to normalize tumor vasculature, decompose stromal barriers, and revert immunosuppression.

Main Methods:

• Literature review of studies investigating oncolytic viruses and the tumor microenvironment.
• Analysis of mechanisms of OV interaction with tumor stroma and immune cells.
• Examination of preclinical and clinical data on TME-targeted OV therapy in pancreatic cancer.

Main Results:

• OVs can be engineered to normalize tumor vasculature, degrade the desmoplastic stroma, and overcome immune suppression within the TME.
• TME-targeted OV therapy demonstrates potential in preclinical models of pancreatic cancer.
• Reversing the immunosuppressive TME is a key mechanism for OV efficacy.

Conclusions:

• Oncolytic virotherapy represents a promising approach for pancreatic cancer by directly targeting the complex tumor microenvironment.
• Further research into TME-manipulating OVs could lead to more effective pancreatic cancer treatments.
• Strategies focusing on OV-mediated TME normalization are critical for improving therapeutic outcomes.