Natural Killer Dendritic Cells in Cancer

描述（由申请人提供）：在啮齿类动物和人类的一些研究已经鉴定出具有裂解和抗原呈递功能的免疫细胞。我们在正常小鼠的多个器官中发现了同时表达自然杀伤细胞（NK）标记物NK1.1和树突状细胞（DC）标记物CD11c的细胞。我们已经确定这些自然杀伤树突状细胞（NKDC）可以溶解肿瘤细胞，呈现肿瘤来源的抗原，并激活na？体外培养T细胞。此外，我们发现激活的NKDC分泌高水平的ifn - γ。总的来说，我们对NKDC知之甚少。通过这一建议，我们将为了解NKDC生物学奠定科学基础。在目的1中，我们将描述NKDC对ifn - γ产生的调节。此外，我们将测试活化和Flt3配体介导的扩增如何影响NKDC表型和功能。在Aim 2中，我们将使用NKDC来预防或治疗小鼠肿瘤。将研究T细胞刺激、NKDC裂解功能和NKDC ifn - γ产生对NKDC抗肿瘤活性的贡献。我们预计我们的发现将阐明这种新型细胞类型如何促进各种免疫过程，以及NKDC如何在癌症治疗中发挥作用。

DESCRIPTION (provided by applicant): A few studies in rodents and humans have identified immunologic cells that possess both lytic and antigen presenting function. We have found cells expressing both the natural killer (NK) cell marker NK1.1 as well as the dendritic cell (DC) marker CD11c, in multiple organs of normal mice. We have established that these natural killer dendritic cells (NKDC) can lyse tumor cells, present tumor-derived antigen, and activate na?ve T cells in vitro. In addition, we have discovered that activated NKDC secrete high levels of IFN-gamma. Overall, though, very little is known about NKDC. With this proposal, we will establish the scientific foundation to understand NKDC biology. In Aim 1, we will delineate the regulation of IFN-gamma production by NKDC. In addition, we will test how activation and Flt3 ligand-mediated expansion each affect NKDC phenotype and function. In Aim 2, we will use NKDC to prevent or treat tumors in mice. The contribution of T cell stimulation, NKDC lytic function, and NKDC IFN-gamma production to the anti-tumor activity of NKDC will be investigated. We anticipate that our findings will elucidate how this novel cell type may contribute to a variety of immune processes and how NKDC may be useful in the treatment of cancer.