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

Emerging evidence has revealed the critical role of the tumor microenvironment (TME) in tumor progression, angiogenesis, metastasis, and immunosuppression. Oncolytic viruses (OVs), a versatile therapeutic agent that targets both cancer cells and the TME, have emerged as a promising candidate for antitumor therapy. Strategies of manipulating OVs against the TME include normalization of the tumor vasculature, decomposition of the tumor stroma, and reversion of the immunosuppressive microenvironment. In pancreatic cancer, desmoplastic stroma comprises up to 80% of the tumor mass, accompanied by hypovascularity and profound immunosuppression, conferring a particularly important role to TME-targeted oncolytic virotherapy. Mechanisms and supporting evidence of OVs reversing the tumor-privileged TME and applications of TME-targeted OVs for pancreatic cancer are summarized in this review.