Dual roles of GM-CSF in modulating NK-cell migratory properties (CAM4P.147)

Background: Natural Killer (NK) cells play a key role in innate immunity against viral, microbial infections and transformed cells and their migration for effector function to peripheral tissues or inflamed lymph nodes are tightly regulated. Of interest, production of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) by cancer cells is correlated to host immune suppression and tumor metastasis, suggesting an immune evasion property of GM-CSF. Here we examined role(s) of recombinant GM-CSF in the regulation of NK-cell migratory properties in vitro. Methods: Previously published “Y” shape microfluidic platform was used to study the roles of GM-CSF gradient on NK-cell migrations. IL-2 activated human primary NK cells were used in the migration studies. Results: Our microfluidic-based migration study demonstrated a novel role of GM-CSF in regulating repulsive NK-cell migration under the stable GM-CSF gradient (at 20 ng/ml), followed by subsequent arrest in cell migration. Blocking of GM-CSF-Rα abolished the repulsive migratory behavior but not the arrest. In contrast, lower concentrations of GM-CSF induced hyper-polarization, immediate arrest of NK cells, and little/or no NK-cell migrations. Circularity measurement in controls and above experiments confirmed statistically the correlation between hyperpolarization and migration arrest. Future analyses will elucidate the mechanisms underlying the dual roles of GM-CSF in the regulation of NK-cell migratory properties.