The central aim of this proposal is to dissect the cellular interaction between NK cells, dendritic cells and tumor cells and to dissect the molecular responses of NK cells to tumor. Essentially we hypothesize that the coordinate interaction of NK and DCs will induce an acute immune response to cancer, reinitiate a new T-cell response, and modify the chronic inflammatory response characteristic of most established human tumors. Ultimately understanding the biology of these processes is hoped to facilitate novel therapeutic approaches in tumor cell killing. These studies will rely on a variety of cutting edge microscopic methods to examine cell cell interaction, antigen presentation by cells, cell trafficking and apoptosis. Therefore a central imaging core is defined as an integral component of this proposal. The Core will be housed in the Center for Biologic Imaging (CBI) of the University of Pittsburgh Medical Center. This Center is equipped to perform a continuum of optical methods including all types of microscopy essential to this Program Project. Within the scope of this Program light microscopic techniques include: conventional histological, immuno-histological, and laser confocal, methods, as well as multiphoton and live cell and tissue imaging technologies. Our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate subtle qualitative changes, and this a major function of the Core in this Program. At the electron microscopic level thin section electron microscopy and immuno-electron microscopic evaluation of specimens as a natural extension of the light microscopic analyses will be employed when needed.
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