Neutrophils are known to be key innate defenders through performing vital and diverse functions such as degranulation, oxidative burst, and generation of extracellular trap (NET). Recent data suggest that neutrophils may also play key roles in modulating tissue inflammatory/immune environment by secreting soluble mediators as well as surface-attached co-activators. Furthermore, neutrophils may adopt distinct functional states either conducive or detrimental for tumor-growth through cellular contact with cancer cells and/or other immune cells such as T helper cells. However, molecular mechanisms that modulate functional adaptations of neutrophils are not well understood. The objective of my thesis is to identify the role of Tollip, a novel TLR signaling adaptor molecule, in modulating neutrophil functions by suppressing the inflammatory signaling pathway. Preliminary data from our lab suggest Tollip deficient neutrophils may be programed to exhibit enhanced anti-tumor activities. Based on these novel findings, I tested the hypothesis that neutrophils also have subsets with different functions similar to monocyte/macrophages, and Tollip deficient neutrophils may be programmed into an enhanced anti-tumor state through upregulating inflammatory signaling processes and mediators. / Ph. D. / Cancer immunotherapy gained instant popularity overnight after former president of the United States, Jimmy Carter, announced successful treatment of his metastatic melanoma. Since then, FDA has approved the first immunotherapy in the summer of 2017. Current cancer immunotherapy focuses heavily on the potential of T cells to target unregulated cells in the host. However, time and specificity have proven a difficult challenge to overcome. Innate immune cells may circumvent these challenges and present equal potential as therapy in the fight against cancer. Neutrophils are one of the innate immune cells that provide first line of defense against pathogens. Neutrophils can clear danger or maintain the situation until more cells arrive to help clear the danger. They were originally thought to confer simple and transient effects, but emerging data suggest they may have more diverse role in host defense. We propose programming neutrophils will make the cells less susceptible to cancer manipulation and provide enhanced protection against cancer establishment and maintenance.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/98571 |
| Date | 04 December 2018 |
| Creators | Lee, Christina K. |
| Contributors | Translational Biology, Medicine and Health, Li, Liwu, Jones, Caroline N., Xu, Bin, Theus, Michelle H. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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