Figure 1.

Tumor microenvironment sensitizes endothelium for OV infection

Upregulation of proangiogenic signaling in a growing tumor makes ECs vulnerable to OV infection via several mechanisms: (1) increased permeability of neovessels facilitates OV accumulation in the perivascular area; (2) actively proliferating ECs provide OVs with ribonucleotide reductase (RR), the enzyme essential for virus replication; and (3) vascular endothelial growth factor (VEGF) binding to VEGFR2 activates transcription repressor PRD1-BF1, which interferes with genes involved in type I interferon (IFN)-mediated antiviral signaling. Additionally, cancer cells and reprogrammed stromal cells create an immunosuppressive milieu favoring OV replication in the tumor microenvironment. In turn, EC infection may promote antitumor responses by (1) secreting proinflammatory cytokines; (2) recruiting/activating immune cells; (3) launching vascular shutdown; and (4) supporting OV spread in the tumor. TAMs, tumor-associated macrophages; CAF, cancer-associated fibroblast; MDSC, myeloid-derived suppressor cell.