Modulation of neutrophil granulocytes in head and neck cancer by tumor-derived macrophage migration inhibitory factor

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In previous studies we have described functional alterations in polymorphonuclear granulocytes (PMN) of patients with head and neck cancer. In patients with advanced disease a strong infiltration of the tumor by PMN was associated with reduced survival. In search of the mechanisms behind these findings, in the proposed project we will investigate the rote of the tumor-derived inflammatory cytokine macrophage migration inhibitory factor (MIF) in the modulation of PMN immunobiology. To this end, we will use in vitro co-culture systems of HNO cells and PMN, human tumor material, and a murine orthotopic HNO model, which has been optimized in preliminary work to this project. We will test the hypothesis that MIF produced by tumor cells alters the function and differentiation of PMN in the tumor host. This functional PMN alteration may promote tumor progression through feed-back mechanisms on the tumor cells.