肿瘤细胞糖酵解能够诱导免疫功能失调，但是其在肝癌中的作用机制尚不清楚。本项目拟在前期已发现SALL4再激活诱导肝癌细胞PD-L1表达的基础上，进一步结合多色流式细胞术和肝脏原位分析等技术，分析SALL4调控肝癌免疫微环境尤其是T细胞表型和功能的作用；通过细胞能量代谢分析以及色谱/质谱技术观察SALL4对肝癌细胞糖酵解的影响；借助肝癌细胞转录组深度测序、qPCR、萤光素酶报告基因以及ChIP实验等多种手段，筛选并鉴定SALL4调控糖酵解的关键靶基因；结合细胞清除、细胞转输及免疫缺陷小鼠寻找SALL4-糖酵解诱导肝癌免疫逃逸的关键细胞；最后，通过联合阻断SALL4-糖酵解功能轴以及PD-1观察抗肿瘤效果。本项目旨在寻找SALL4诱导糖酵解重编程导致免疫逃逸的分子机制和细胞机制，为肝癌的治疗提供新的思路和治疗策略。

Cancer cells exhibit aberrant glucose metabolism, which cause dysfunction of tumor infiltrating immune cells. The underlying molecular mechanisms are complex and have not been fully explained in Hepatocellular carcinoma cells (HCC). Our previous study found that SALL4 re-activation in HCC could promote PD-L1 expression, and this project intends to explore whether SALL4 could regulate glucose metabolic reprogramming and then affect immune microenvironment of HCC using FACS. Then, the effect of SALL4 on glycolysis of HCC will be observed using cell energy metabolism analysis and chromatography/mass spectrometry. The key target genes of SALL4 will be screened and identified using transcriptome sequencing, qPCR, fluorescein reporter gene and ChIP assay. Furthermore, the key immune cell induced by SALL4-glycolysis will be searched by cell deletion and cell transfer in vivo. Finally, the anti-HCC effect will be observed by blocking SALL4-glycolysis axis and PD-1 in vivo. The aim of this project is to reveal the molecular and cellular mechanisms of immune escape induced by SALL4-glycolysis reprogramming, and then to improve anti-HCC immune response by regulating the metabolism. The findings of this study will provide new ideas and strategies for the treatment of HCC.