Modulation of Neutrophil Functions and Anti-Tumor Immune Responses by Innate Suppressors

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.