非小细胞肺癌严重威胁人类健康。近年来免疫检查点成为非小细胞肺癌中研究热点，但其机制尚未完全解析。因此，进一步探讨免疫检查点关键分子调控免疫作用并寻找有效的治疗策略具有临床意义。近来报道称CMTM6维持肿瘤细胞表面PD-L1表达，然而，关于CMTM6是否参与肿瘤自噬调控尚不清楚。本课题组前期研究发现CRISPR-cas-CMTM6可诱导肺癌细胞保护性细胞自噬，其机制依赖于敲除CMTM6后明显抑制Akt-mTOR信号，我们推测CRISPR-cas-CMTM6联合自噬抑制剂可能提高抗肿瘤疗效。本实验拟通过体内外实验证实靶向编辑CMTM6诱导肺癌细胞发生保护性自噬作用机制，通过免疫印迹实验检测Cas-CMTM6质粒抑制自噬上游关键信号通路Akt/mTOR，研究干预或后续治疗策略，为临床治疗策略的制定提供研究思路。

Non-small cell lung cancer poses a serious threat to human health. In recent years, immune checkpoints have become a research hotspot in non-small cell lung cancer, but the mechanism has not been fully resolved. Therefore, it is of clinical significance to further explore the key molecules of immune checkpoints to regulate immunity and find effective therapeutic strategies. Recently, it has been reported that CMTM6 maintains the expression of PD-L1 on the surface of tumor cells. However, it is unclear whether CMTM6 is involved in the regulation of tumor autophagy. Our previous study found that CRISPR-cas-CMTM6 can induce autophagy in non-small cell lung cancer cells, and its mechanism relies on knockout of CMTM6 to significantly inhibit Akt-mTOR signaling. We speculate that CRISPR-cas-CMTM6 combined with autophagy inhibition may improve the anti-tumor effect. This experiment is to confirm the mechanism of protective autophagy induced by targeted editing of CMTM6 in non-small cell lung cancer cells in vitro and in vivo experiments and provide effective research ideas for the development of clinical treatment strategies.