The Type I Interferon Anti-Viral Pathway Contributes To Macrophage Polarization Following Infection With Oncolytic Vesicular Stomatitis Virus

Vesicular stomatitis virus (VSV) is a promising oncolytic agent that directly kills cancer cells, but which also modulates immune elements within the tumor microenvironment. Here we were interested in how VSV affects tumor-associated macrophages (TAMs), a cell type that interconverts along a spectrum of polarizations from pro-cancer M2 to anti-cancer M1 subtypes. We hypothesized that VSV infections would switch M2 TAMs to an M1 phenotype via activation of the type I interferon anti-viral response. Such was the case with a mutant strain of VSV (rM51R-M) where the lack of a functional M protein led to activation of the anti-viral response and the upregulation of M1 markers (i.e. IFNa, STAT1, P-STAT1, MHC-II, and CD80, but not IRF5) in model M2 THP-1 macrophages. Our data suggest that rM51R-M virus has a previously unappreciated immunogenic potential based on modulation of TAM phenotypes.