EBNA2/miR-214/Galectin-3途径抑制NKp30+NK细胞功能在EBV+DLBCL免疫逃逸中的作用及机制研究

免疫逃逸在EB病毒(EBV)阳性弥漫大B细胞淋巴瘤（EBV+DLBCL）的发生和发展中发挥重要作用，但具体机制未明。我们前期研究发现，在EBV+DLBCL患者中，具有更强抗EBV作用的NKp30+NK细胞的功能显著降低；机制研究发现，Galectin-3是导致NKp30+NK细胞功能减低的关键分子,EBV核抗原EBNA2缺失导致miRNA-214下调可能是Galectin-3上调的上游途径。因此我们推测：在EBV+DLBCL中，EBNA2/miR-214/Galectin-3途径通过抑制NKp30+NK细胞功能实现其免疫逃逸。本课题拟从分子、细胞、动物和临床水平进一步明确证实改假设，其完成将为EBV+DLBCL治疗提供新的靶点和策略。

Immune escape plays a critical role in the development and progression of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (EBV+DLBCL), but the underlying mechanism remains unclear. Our previous study found that NKp30+NK cells, innate lymphocytes important for anti-EBV, become severely functionally impaired in EBV+DLBCL. Further study found that Galectin-3 was a key molecule which induced functional inhibition of NKp30+NK cells, and lacking of EBV nuclear antigen EBNA2 followed by down-regulation of miRNA-214 may upregulate Galectin-3. Therefore, we hypothesized that EBNA2/miR-214/Galectin-3 pathway promoted EBV+DLBCL to escape from immune surveillance via inhibiting NKp30+NK cell function. Experiments in vitro and vivo were designed to verify the hypothesis mentioned above. The fulfillment of this project would provide potential immune targets and novel treatment strategy for EBV+DLBCL.