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

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Austin Grant Simmons (Creator)
Institution
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/
Advisor
Maryam Ahmed

Abstract: 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.

Additional Information

Publication
Thesis
Simmons, A. (2021). Vesicular Stomatitis Virus Suppresses The Phagocytic Capacity Of A Tumor-Promoting Macrophage Population. Unpublished Master’s Thesis. Appalachian State University, Boone, NC.
Language: English
Date: 2021
Keywords
Vesicular stomatitis virus, Macrophages, Oncolytic virotherapy, Phagocytosis, Tumor microenvironment

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