甲胎蛋白调控PD-L1/PD-1表达对肝癌细胞免疫逃逸的影响及其作用机制

近期研究显示肝癌细胞的甲胎蛋白（AFP）与程序死亡配体-1（PD-L1）高表达呈正相关性。癌细胞高表达PD-L1导致免疫逃逸，PI3K/AKT信号途径被激活后能促进癌细胞的PD-L1表达。AFP是肝癌细胞高特异性表达的蛋白质，我们前期研究发现AFP能激活PI3K/AKT信号途径，暗示AFP具有促进癌细胞PD-L1表达的作用，提示AFP在肝癌细胞免疫逃逸中发挥关键性作用。但是AFP如何调节癌细胞和免疫细胞的PD-L1/PD-1表达目前并不清楚。我们提出“AFP通过调节癌细胞和免疫细胞PD-L1/PD-1的表达促进肝癌细胞免疫逃逸”的科学假说。本项目通过检测肝癌患者癌组织和免疫细胞的PD-L1/PD-1表达与AFP表达的相关性，以及AFP对PD-L1/PD-1表达的调控作用及其机制，探索AFP在肝癌细胞免疫逃避所发挥的作用，对发现AFP的新功能和肝癌免疫治疗具有重要的学术意义和应用价值。

Previously, documents evidences indicated that the expression of alpha fetprotein(AFP) correlated positively with programmed death ligand-1(PD-L1) in hepatocellular carcinoma(HCC) cells. The high expression of PD-L1 lead to immune escape of cancer cells, the activation of phosphatidylinositol 3-kinase (PI3K)/AKT pathway was able to promote expression of PD-L1 in cancer cells. AFP is a specific protein that high expressed in HCC cells, recently, we studied found that AFP harbors a function to activate PI3K/AKT signal pathway, this implicated that AFP has a role to stimulate expression of PD-L1 in cancer cells, and AFP plays a pivotal role in promoting immune escape of cancer cells. How to AFP regulates the expression of PD-L1/PD-1 in immune cells and cancer cells is still unclear. We hypothesis that “AFP stimulates HCC cells escape immunesurveillance through regulating expression of PD-L1/PD-1 in immune cells and cancer cells”. In the project, we aim to detect the expression of PD-L1/PD-1 corrects with the expression of AFP in HCC cell and immune cells, and also analyze AFP regulates the expression of PD-L1/PD-1, to explore the role mechanism of AFP in HCC escape immunosurveillance. The study will find the novel function of AFP, and AFP is applied as a new biotarget for the immunotherapy of HCC patients.