BDCA1阳性炎性树突状细胞在非小细胞肺癌免疫调节平衡中的作用及机制

树突状细胞（DC）是人体内功能最强的抗原提呈细胞，在诱导高效、特异的抗肿瘤细胞免疫中起关键作用。区别于传统DC，一种来源于单核细胞，表达BDCA1的新型炎性树突状细胞（infDCs）亚群可能具有独特的抗肿瘤免疫活性。前期研究中发现，NSCLC患者胸水中存在BDCA1+infDCs，该细胞可促进CD4+T细胞分化为Th17细胞，且与Treg细胞相互拮抗。推测该炎性DC可能通过调控Th17/Treg的发生、分化来影响肿瘤免疫调节的平衡。我们将在此基础上进行：（1）人类BDCA1+infDCs体外功能研究；（2）探讨BDCA1对BDCA1+infDCs免疫功能的影响；（3）明确CSF-1R信号对BDCA1+infDCs分化的影响，及该细胞分化、功能的关键转录因子，结合到BDCA1基因的启动子区域；（4）确定其体内介导抗NSCLC免疫反应的机制研究。为寻找新的NSCLC免疫治疗手段提供理论依据。

Dendritic cells (dendritic cell, DC) is the most powerful antigen-presenting cells in human, and it plays a key role in the the induction of specific and efficient anti-tumor cellular immunity.Different from the traditional DC, one derived from the mononuclear cells and expressed BDCA1 novel inflammatory dendritic cells (infDCs) may have a unique anti-tumor immune activity.BDCA1 + infDCs is found in both NSCLC tumor tissue and pleural effusion.It can induce CD4+T cell differentiate to Th17 cell. BDCA1 + infDCs and Treg cells are mutually antagonistic.We speculate the inflammatory DCs may control the tumor immunoregulatory balance by regulating the development and differentiation of Th17 and Treg cell.This study will extend our previous works and will (1) analyze the human BDCA1+ infDCs vitro functional;(2) clear the impact of BDCA1 in BDCA1 + infDCs immune function; (3) define the influence of the CSF-1R signal in BDCA1 + infDCs differentiation,and make sure the key transcription factor and the promoter region combined to BDCA1 gene; (4) determine its mechanism mediated anti-NSCLC immune response. We will provide a theoretical basis for new means of NSCLC immunotherapy.