Jessica McCanless wins Melton Award

Jessica McCanless, a graduate student who works with Dr. Maryam Ahmed and Dr. Darren Seals, won the Thoyd Melton Award at this year's North Carolina Branch of the American Society for Microbiology annual meeting. The Thoyd Melton Award was established to recognize an outstanding oral presentation by a graduate student.  Jessica is the first ever Appalachian State student to win this award. Jessica's presentation was on her research into oncolytic (cancer-killing) viruses as a treatment option for breast cancer.  

Breast tumors have a variety of non-tumor cells associated with them, including tumor-associated macrophages (TAMs), which tumors can influence to promote cancer cell growth, survival, and invasion. Cancers that have a high number of wound-healing, pro-tumor (M2) TAMs associated with them have a high risk of becoming metastatic, and thus such cancers have poorer patient outcomes than those with an anti-pathogenic, anti-tumor TAM (M1) population. It has been shown that the use of oncolytic (cancer-killing) viruses can promote tumor clearance and have the potential to alter a patient’s own immune system to seek out and destroy tumors which have metastasized, or spread to distant sites. Therefore, the Ahmed/Seals Lab seeks to develop Vesicular Stomatitis Virus (VSV), specifically an immunogenic mutant rM51R-M, as an immunotherapy for metastatic breast cancer by assessing the virus’ effect on TAMs. Jessica’s project involves co-culturing M2 macrophages with invasive breast cancer cells, infecting the co-cultures with VSV, and then measuring the changes in chemical signals (cytokines) that are produced by the cells. Each macrophage type has its own signature profile of cytokines it produces, with M2 TAMs producing anti-inflammatory cytokines (IL-10) to promote wound healing and tissue repair, and M1 TAMs producing pro-inflammatory cytokines (IL-6 and TNFα) to promote immune surveillance and abnormal cell and pathogen clearance. If the co-cultures show changes in cytokine secretion upon infection with the virus, with increases in the pro-inflammatory cytokines and decreases in the anti-inflammatory cytokines secreted, then that suggests the pro-tumor, M2-like TAMs are becoming more anti-tumor, or M1-like. Upon infection with rM51R-M virus, co-cultures of invasive breast cancer cells and M2 macrophages showed almost a 3-fold increase in the secretion of the pro-inflammatory cytokine TNFα and about a 50% decrease in the secretion of the anti-inflammatory cytokine IL-10. The data also suggests that these changes are due to macrophage responses to infection by rM51R-M, not the breast cancer cells, and it is hypothesized that this is due to the upregulation of M1-associated antiviral pathways (type I Interferon). These results support the hypothesis that rM51R-M promotes changes in TAM populations that result in systemic anti-tumor activity. Further studies will involve determining the mechanism by which the virus exerts its effects (i.e. inducing  the type I Interferon pathway) and verifying that the M2 macrophages are indeed changing their functioning to behave in a more M1-like manner.

 Jessica grew up in North Carolina and received her undergraduate degree at UNC Greensboro, with a BS in Biology and minors in Chemistry and Psychology. She also earned the Award for Excellence in Scholarship for STEM at the Annual Graduate Student Symposium held at the College of William and Mary in the spring of 2018.

Jessica McCanless
Published: Nov 5, 2018 11:03am