Natural Killer Dendritic Cells in Cancer

癌症中的自然杀伤树突状细胞

• 批准号: 7156378
• 负责人: Bryan Michael Burt
• 金额: $ 5.04万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-07 至 2008-07-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156378
• 关键词: antigens; dendritic cells; neoplasm /cancer

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.

描述(申请人提供)：在啮齿动物和人类身上的一些研究已经确定免疫细胞同时具有裂解和抗原提呈功能。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NK1.1和树突状细胞(DC)标记CD11c的细胞。我们已经证实，这些自然杀伤细胞树突状细胞(NKDC)在体外可以溶解肿瘤细胞，提呈肿瘤衍生抗原，并激活原始T细胞。此外，我们还发现活化的NKDC分泌高水平的干扰素-γ。但总体而言，人们对NKDC知之甚少。有了这一建议，我们将为理解NKDC生物学奠定科学基础。在目标1中，我们将描述NKDC对干扰素-γ产生的调节。此外，我们还将测试激活和Flt3配体介导的扩增对NKDC表型和功能的影响。在目标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的溶解功能和NKDC产生的干扰素-γ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的细胞类型如何对各种免疫过程做出贡献，以及NKDC如何在癌症治疗中发挥作用。