The function and phenotype of intrahepatic CD8+ TRM cells in 35 HCC patients were analyzed using multicolor flow cytometry. Using a tissue microarray of 80 HCC patients, we performed the prognosis analysis. Moreover, we investigated the suppressive effect of FGL1 on CD8+ TRM cells both in in vitro induction model and in vivo orthotopic HCC mouse model.
There was an increase in LAG3 expression in CD8+ TRM cells in end-stage HCC; moreover, FGL1 levels were negatively correlated with CD103 expression and related to poor outcomes in HCC. Patients with high CD8+ TRM cell proportions have better outcomes, and FGL1-LAG3 binding could lead to the exhaustion of CD8+ TRM cells in tumors, indicating its potential as a target for immune checkpoint therapy of HCC. Increased FGL1 expression in HCC may result in CD8+ TRM cell exhaustion, causing tumor immune escape.
We identified CD8+TRM cells as a potential immunotherapeutic target and reported the effect of FGL1-LAG3 binding on CD8+ TRM cell function in HCC.
使用多色流式细胞术分析了35例HCC患者肝内CD8TRM细胞的功能和表型。使用80例HCC患者的组织微阵列,我们进行了预后分析.此外,我们在体外诱导模型和体内原位HCC小鼠模型中研究了FGL1对CD8TRM细胞的抑制作用。
在晚期HCC的CD8+TRM细胞中LAG3表达增加;此外,FGL1水平与CD103表达呈负相关,与HCC不良预后相关。高CD8+TRM细胞比例的患者有更好的结果,FGL1-LAG3结合可导致肿瘤中CD8+TRM细胞耗尽,表明其作为肝癌免疫检查点治疗靶点的潜力。肝癌中FGL1表达增加可能导致CD8+TRM细胞衰竭,导致肿瘤免疫逃逸。
我们将CD8+TRM细胞确定为潜在的免疫治疗靶标,并报道了FGL1-LAG3结合对HCC中CD8+TRM细胞功能的影响。