Vesicular Stomatitis Virus Suppresses The Phagocytic Capacity Of A Tumor-Promoting Macrophage Population

Tumor-associated macrophages (TAMs) have been found in high numbers in aggressive breast cancers, where they often stimulate metastasis and suppress anti-tumor immunity. Such TAMs represent the alternatively activated M2 subtype, though they may exist as classically activated M1 macrophages with anti-tumor phenotypes. The purpose of this project was to evaluate the impact of oncolytic vesicular stomatitis virus (VSV) on M1 and M2 macrophages by a determination of changes to their phagocytic properties. THP-1 monocytes were differentiated and polarized to M1 or M2 macrophage subtypes and infected with a recombinant wild-type strain of VSV (rwt) or an isogenic matrix (M) protein mutant strain (rM51R-M virus), the latter of which stimulates antiviral immunity. Our data indicate that M2 macrophages phagocytose 11-fold more E. coli bioparticles than their M1 counterparts, and that infection with rwt virus, and to a lesser degree rM51R-M virus, reduces phagocytosis to M1 macrophage levels. To determine whether changes in phagocytosis might occur in a cancer context, we developed an in vitro breast tumor model containing dye-labeled MDA-MB-231 breast cancer cells and pre-polarized M2 macrophages. By elucidating how macrophages and cancer cells collectively respond to VSV, we hope to gain a greater understanding of VSV as an anti-cancer agent.