树突状细胞(DC)是目前已知功能最强的专职抗原呈递细胞，基于DC的抗肿瘤免疫治疗被认为是最有运用价值的方法之一，但是在肿瘤微环境的作用下影响其作用。为此，研究肿瘤微环境中产生的活性氮（ONOO−）对DC分化、成熟和免疫功能的影响以及硒和硒蛋白在氧化应激条件下对DC功能的保护作用非常重要。本项目将采用RNA干扰、抑制信号通路等手段，在细胞和分子水平上研究MAPK信号通路在ONOO− 诱导的DC免疫功能和迁移能力改变中的作用，探讨硒和DC免疫功能、迁移能力之间的关系，揭示细胞内氧化还原平衡、iNOS 和Ca2+ 水平变化在硒诱导的DC免疫功能和迁移能力中的作用机理，重点研究硒蛋白基因沉默对氧化应激条件下DC免疫功能和迁移能力的影响及其机理。本研究对于全面认识硒在免疫系统中的生物学功能具有十分重要的科学意义，而且可能为硒在DC肿瘤疫苗中的应用提供新的思路和实验依据。

Dendritic cells (DC) are at the centre of the immune system that function as professional antigen presenting cells. DC-based tumor vaccines is considered one of the ways to conquer cancer, however, its therapeutic effect is not ideal due to the formation of tumor microenvironment. Therefore, this study will focus on the effect of peroxynitrite on the differentiation, maturation and immune function of DC, and the protective effect of selenium and selenoproteins on the function of DC under oxidative stress by RNA interference and inhibition of signaling pathways. First, the role of MAPK signalling pathway on the change of ONOO−-induced immune function and migration in DC will be investigated, then the relationship between selenium and the immune function and migration of DC, and the effect of intracellular redox balance, iNOS and Ca2+ levels on selenium-induced immune function and migration in DC will also be studied. Furthermore, the effect of selenoprotein gene silencing on peroxynitrite-induced immune function and migration disruption in DC will be observation. This study will help us to understanding the biological functions of selenium in immune system, and may provide new ideas and experimental evidence for selenium in DC-based tumor vaccines.