常规治疗手段未能有效提高肺癌5年生存率，主要是因为肺癌干细胞对治疗的抵抗。有效清除肺癌干细胞对治疗至关重要，但目前尚没有找到有效方法。我们前期研究发现在肺癌切除标本中，NK细胞与肺癌干细胞呈负相关。结合前期研究结果及相关文献报道，我们推测NK细胞具备清除肺癌干细胞的潜能。NK细胞表面TIGIT蛋白高表达，导致NK细胞功能缺失，阻断TIGIT蛋白可增强NK细胞的杀伤作用。本项目拟通过阻断免疫检查点TIGIT来提高NK细胞对非小细胞肺癌干细胞的杀伤作用：明确TIGIT抗体在不同小鼠模型中激活NK细胞的作用机制；确定活化的NK细胞对肺癌干细胞的杀伤作用；进一步探索NK细胞与肺癌干细胞相互作用过程中关键的信号通路及相关细胞因子的变化，以期找到新的治疗靶点。本项目研究结果将为通过免疫治疗清除肺癌干细胞的方法提供理论依据和研究基础。

Conventional treatments can not effectively improve the 5-year survival rate of lung cancer, mainly because of the resistance of lung cancer stem cells to treatment. Completely removal of lung cancer stem cells is very important prolong the survival of lung cancer, but up to date there is no effective method to remove lung cancer stem cells. Our previous studies found that NK cells were negatively correlated with lung cancer stem cells in non-small cell lung cancer resection specimens. Combined with the previous research results and related literature, we speculate that NK cells have the potential of scavenging lung cancer stem cells. The high expression of TIGIT protein on NK cells results in the exhausttion of NK cell function. Blocking TIGIT protein can enhance the killing effect of NK cells. This project intends to enhance the killing effect of NK cells on NSCLC stem cells by blocking TIGIT, an immune checkpoint, to clarify the mechanism of activating NK cells by TIGIT antibodies in different mouse models; to determine the killing effect of activated NK cells on lung cancer stem cells; and to further explore the key signaling pathways and related cellular factors in the interaction between NK cells and lung cancer stem cells. The results of this project will provide theoretical basis and research basis for the method of eliminating lung cancer stem cells through immunotherapy.