The Cytotoxic Effects Of Vesicular Stomatitis Virus On THP-1 Macrophages

Cancer cells do not act autonomously. The interaction between cancer cells and other ‘normal’ cell types creates a tumor microenvironment conducive for the growth and progression of the disease. Tumor-associated macrophages (TAMs) are among the immune cell types that accumulate in cancerous tissue. M1-like TAMs may target and kill cancer cells. M2-type TAMs generate the growth factors that support cellular growth, angiogenesis, and metastasis. Vesicular stomatitis virus (VSV) can target cancer cells, but its effect on TAMs is unclear. Here, model THP-1 monocytes were polarized into M0, M1, or M2 macrophages to measure their response to infection with wild-type (rwt) and nonvirulent mutant (rM51R-M) strains of VSV. M1 macrophages were insensitive to VSV infection. No cells showed evidence of viral replication (measured by GFP-positivity), and viability was not statistically different from that of mock-infected cells. M2 macrophages, in contrast, were highly susceptible to viral replication, particularly to the rwt strain where maximal viral replication (36% of cells were GFP-positive) and cytotoxicity (31.3% viability relative to mock infection) occurred under a synchronous infection parameter of 10 plaque-forming units per cell. M2 macrophage susceptibility to oncolytic VSV suggests newfound benefits for anti-cancer virotherapies targeting pro-tumor TAM populations