γδT细胞具良好的肿瘤杀伤能力，但白血病细胞往往通过免疫逃逸机制逃避γδT的免疫攻击，限制其临床应用。近年来自噬成为生物学领域研究热点，对肿瘤发生、耐药、转移的调控作用较为明确，自噬是否在白血病逃逸γδT杀伤过程中发挥作用尚无研究。本项目立足前期成果“γδT杀伤白血病细胞的关键是白血病细胞ULBP4的表达以及NKG2D-ULBP4的识别”，发现抑制白血病细胞自噬促进了γδT对其免疫清除，同时诱导了胞膜ULBP4的表达，推测白血病细胞可能通过自噬调控ULBP4而逃逸γδT的杀伤。项目在细胞及动物水平上，通过siRNA干扰ATG5/ATG12或采用药物阻断白血病细胞自噬，观察γδT对其杀伤作用；通过电镜、免疫荧光、免疫共沉淀等技术分析自噬-溶酶体系统对ULBP4蛋白的转录后调控机制（直接降解、抑制向胞膜转运、或sULBP产生）及信号通路；为提高γδT杀伤效率，推动γδT的临床应用提供实验依据。

γδT cell is powerful in killing various tumor cells，but some immune escape mechanisms protect leukemia cells from γδT attack in vivo, which limits γδT clinical application. Recently, autophagy has become a hot spot in the field of biological research. It is very clear that autophagy is envolved in tumorigenesis, metastasis and drug resistance, however, it is unknown whether autophagy plays a role in the process of leukemia cells evading γδT-mediated killing. Our previous study have revealed that ULBP4 on leukemia cell is determinant of recognition and killing by γδTcell. We also found that inhibition of autophagy can enhance leukemia cell susceptibility to γδT-mediated lysis in vitro, and meanwhile increase the expression level of ULBP4. These findings indicates that leukemia cells evade effective γδT-mediated killing by activating autophagy. This study will use siRNA-ATG5/ATG12 or drugs to block leukemia cell autophagy, and observe the killing effect of γδT, both in vivo and in vitro; clariy the post-transcriptional regulation mechanism of ULBP4 protein by autophagy lysosomal system, such as direct lysis , inhibition of translocation to the cell membrane, or inducing sULBP production, via electron microscopy, immunofluorescence, immuno co-precipitation; try to seek an efficient way to sensitize leukemia to γδT cell, and provide evidence that targeting autophagy may pave the way to achieve more effective γδT-based anti-leukemia immunotherapy.