Therapeutic Targeting Of Macrophage Populations By Oncolytic Vesicular Stomatitis Virus

The human immune system is dedicated to ridding the body of foreign pathogens. However, in the context of cancer members of the innate and adaptive immune systems, M2 macrophages in particular, contribute to tumor growth and metastasis and are thus associated with poor patient prognosis. Metastasis is defined by the acquired ability of cancer cells to invade surrounding tissues and vasculature and is completed upon colonization of distant sites. As these patients respond poorly to traditional treatment options, the need for additional therapies has emerged. The therapies of interest in this thesis are oncolytic viruses that kill cancer cells while sparing healthy cells. This includes oncolytic vesicular stomatitis virus, which has not only demonstrated tumoricidal capabilities, but the ability to modulate immune cells to elicit anti-viral responses. This thesis seeks to investigate if different strains of this oncolytic virus, a recombinant wild-type (rwt) virus and a matrix (M) protein mutant (rM51R-M) virus, can infect and target pro-tumor M2 macrophages and inhibit their stimulatory role in cancer growth and metastasis. To explore this objective, monocytes, M0, M1, and M2 macrophages were infected with rwt virus or rM51R-M virus whereupon viral replication, cell death, phenotypic switching, and podosome formation were analyzed.