H. Lee Moffitt Cancer Center and Research Institute Tampa United States
The goal of this application is to investigate how a microRNA, namely miR183, can disrupt the expression of a critical molecule, DAP12, that controls tumoricidal function in human Natural Killer NK Cells and to understand how nicotine, contained in tobacco smoke, utilizes this mechanism to abort immunity against lung cancer. In addition, we seek to explore the viability of targeting miR183 to restore NK cells as a new form of immunotherapy for early stage lung cancer. We have encountered problems with nicotine instability and work is still in progress to identify conditions to probe the effect of nicotine on NK cells. However, nicotine instability is not an issue in vivo and we have collected blood samples from tobacco smokers, e-cigarette users and past smokers to compare with never smokers for NK function. In terms of anti-miR183 therapeutics, we found that PLGA nanoparticles are readily taken up by NK cells but do not enter the lysosome, thus are not degraded within the NK cell. Nanoparticles will next be loaded with anti-sense miR183 to confirm that NK cell preloaded with anti-miR183 will resist TGFb suppression.