套细胞淋巴瘤（MCL）是一种侵袭性B细胞非霍奇金淋巴瘤，具有不可治愈性，但其发病机制尚不清楚。我们前期研究发现：转录因子SOX11在MCL患者中广泛表达，SOX11低表达患者预后较差。小鼠模型观察到：敲低SOX11的MCL细胞株成瘤能力增强，且肿瘤组织中NK细胞减少。应用细胞因子芯片检测发现：敲低SOX11的MCL细胞株能下调NK细胞趋化因子CCL5的表达。这些结果提示：SOX11可能通过调控CCL5招募NK细胞发挥抗肿瘤功能。本项目拟结合临床样本和实验模型：1）评价MCL中SOX11、CCL5和NK细胞的临床相关性；2）明确SOX11阳性肿瘤细胞招募NK细胞介导的抗肿瘤功能；3）阐明SOX11调控CCL5表达对NK细胞表型/功能的影响和作用机制；4）探讨激活NK细胞抑制MCL进展的临床应用前景。所得结果有望揭示SOX11在免疫调控中的作用机制，为抗肿瘤免疫治疗提供新的思路。

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma, which is uncurable at present, but the pathogenesis of MCL is still unclear. Our previous study indicated that SOX11, a transcription factor, is widely expressed in conventional MCL, but low mRNA expression of SOX11 predicted a poor prognosis in patients with MCL. In a NOD/SCID subcutaneous xenograft model, SOX11 knockdown in MCL tumor cells promoted the tumor growth. Notably, compared with control group, the proportion and the number of natural killer cells (NK cells) in tumor tissues decreased in SOX11 knockdown group. In vitro experiment, by using Cytokine Protein Array kit, we found that the expression of CCL5 was down regulated in SOX11 knockdown tumor cells as compared with control. CCL5 has been shown to be involved in the trafficking of NK cells into the tumor bed. Therefore, these data suggested that high expression of SOX11 in MCL tumor cells could promote NK cell infiltration and activation by increasing CCL5 expression by tumor cells. Based on these results, we will combine the clinical sample analysis, experimental studies and mouse model to: 1) Evaluate the clinical relationship among SOX11, CCL5 and NK cells in MCL tumor tissues; 2) Define the interplay between SOX11 positive tumor cells and NK cells in the pathogenesis of MCL; 3) Understand the mechanism of SOX11 regulated the CCL5 expression in MCL tumor cells and their role in NK cell recruitment and activation; 4) Explore the therapeutic potential of NK cell activation in MCL.The results obtained from this project will not only unveil the new mechanisms of SOX11 affecting the immune response, but also provide a novel strategy for anti-tumor immune therapy by activating NK cells.