脑胶质瘤中协同刺激分子B7-H6调控NK细胞抗肿瘤作用机制

Natural killer (NK) cells play an important immune surveillance role in the occurrence and metastasis of glioma, while activation of NK cells is regulated by costimulatory molecule B7-H6. Our studies have demonstrated that high level of B7-H6 expression in cancer tissue was correlated with distant metastasis, stage and poor prognosis. But the mechanism of B7-H6 promoting glioma progression remains unclear. .Based on previous studies, this project presumes that soluble B7-H6 may competitively bind to its ligand NKp30 thus inhibiting activation of NK cells, promoting glioma progression. We will investigate the expression of B7-H6 and surface receptors of NK cells in glioma tissues, and explore their clinical significances. We also attempt to explore immunological role of B7-H6 in tumor microenvironment of glioma via experiments both in vitro and in vivo, leading to a novel therapeutic strategy of glioma.

自然杀伤(natural killer,NK)细胞在脑胶质瘤的发生与进展过程中发挥重要的免疫监视作用，而NK细胞的活化受胞膜型及可溶型协同刺激分子B7-H6的调控。我们研究发现B7-H6在脑胶质瘤组织中高表达，其表达水平与患者肿瘤分期及不良预后密切相关。但B7-H6在脑胶质瘤发生发展中的作用机制尚未明确。.鉴此，我们提出科学假说：可溶型B7-H6分子竞争性抑制B7-H6/NKp30通路抑制NK细胞活化，促进脑胶质瘤进展。本课题拟通过临床分析B7-H6及NK细胞表面相关受体在脑胶质瘤组织中的表达及意义，体外及体内实验探索B7-H6在脑胶质瘤免疫微环境中的作用，揭示B7-H6在促进脑胶质瘤进展中可能的免疫机制，旨为脑胶质瘤免疫治疗新策略提供理论依据。

自然杀伤(natural killer,NK)细胞在脑胶质瘤的发生与进展过程中发挥重要的免疫监视作用，而NK细胞的活化受协同刺激分子B7-H6的调控。.自2019年获得国家自然基金青年项目资助以来，项目组结合临床研究与实验室研究，揭示B7-H6在促进脑胶质瘤进展中的意义和可能的分子机制，具体体现在(1)完成了协同刺激分子B7-H6分子在脑胶质瘤中相关性及临床意义研究，证实B7-H6在脑胶质瘤组织高表达且与临床WHO分级、病理类型与组织类型相关。(2)体外实验验证了B7-H6分子的表达对脑胶质瘤生物学功能的影响；下调B7-H6表达后胶质瘤细胞系增殖、侵袭能力下降，凋亡增加，细胞周期发生阻滞。而过表达B7-H6表达后胶质瘤细胞系增殖、侵袭能力上升，凋亡下降，细胞周期呈现增殖期改变。(3)构建小鼠脑胶质瘤动物模型，研究干扰B7-H6后小鼠肿瘤生物学功能的变化。B7-H6表达下调后胶质瘤成瘤下降、生物学功能受到影响。