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

在以前的研究中，我们描述了头颈癌患者多形核粒细胞（PMN）的功能改变。在疾病晚期患者中，PMN对肿瘤的强烈浸润与生存率降低有关。为了寻找这些发现背后的机制，在拟议的项目中，我们将研究肿瘤来源的炎症细胞因子巨噬细胞迁移抑制因子（MIF）在PMN免疫生物学调节中的作用。为此，我们将采用HNO细胞与PMN、人肿瘤材料和小鼠原位HNO模型的体外共培养体系，该体系在本项目前期工作中已经进行了优化。我们将验证肿瘤细胞产生的MIF改变肿瘤宿主中PMN的功能和分化的假设。这种功能性PMN改变可能通过对肿瘤细胞的反馈机制促进肿瘤进展。

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.