PDF(Pubmed)
Abstract：
In the tumor microenvironment (TME), CD8+ T cells showed stage exhaustion due to the continuous stimulation of tumor antigens. To evaluate the status of CD8+ T cells and reverse the exhaustion is the key to evaluate the prognosis and therapeutic effect of tumor patients. The aim of this study was to establish a prognostic signature that could effectively predict prognosis and response to immunotherapy in patients with hepatocellular carcinoma (HCC). We used univariate Cox analysis to obtain transcription factors associated with CD8+ T cell exhaustion from The Cancer Genome Atlas dataset. Then, the prognostic signature for transcription factors basic leucine zipper ATF-like transcription factor, Eomesodermin, and T-box protein 21 regulating T cell exhaustion was constructed using LASSO Cox regression. The relative expression levels of the mRNA of the 3 transcription factors were detected by reverse transcription-quantitative polymerase chain reaction in 23 pairs of HCC and paracancer tissues, and verified internally in The Cancer Genome Atlas dataset and externally in the International Cancer Genome Consortium dataset. Cox regression analysis showed that risk score was an independent prognostic variable. The overall survival of the high-risk group was significantly lower than that of the low-risk group. The low-risk group had higher immune scores, matrix scores, and ESTIMATE scores, and significantly increased expression levels of most immune checkpoint genes in the low-risk group. Therefore, patients with lower risk scores benefit more from immunotherapy. The combination of the 3 transcription factors can evaluate the exhaustion state of CD8+ T cells in the TME, laying a foundation for evaluating the TME and immunotherapy efficacy in patients with HCC.
摘要：
在肿瘤微环境（TME）中，由于肿瘤抗原的持续刺激,CD8+T细胞显示出阶段耗尽。评估CD8+T细胞状态并逆转耗竭是评估肿瘤患者预后和治疗效果的关键。这项研究的目的是建立一个预后标志，可以有效地预测肝细胞癌（HCC）患者的预后和免疫治疗反应。我们使用单变量Cox分析从癌症基因组图谱数据集获得与CD8+T细胞耗尽相关的转录因子。然后，转录因子碱性亮氨酸拉链ATF样转录因子的预后特征，Eomesodermin,利用LASSOCox回归构建了调节T细胞衰竭的T-box蛋白21。采用逆转录-定量聚合酶链反应法检测23对肝癌和癌旁组织中3种转录因子mRNA的相对表达水平,并在癌症基因组图谱数据集中进行内部验证，在国际癌症基因组联盟数据集中进行外部验证。Cox回归分析显示风险评分是独立的预后变量。高危组的总生存期明显低于低危组。低危组有较高的免疫评分，矩阵得分，和估计分数，低危组中大多数免疫检查点基因的表达水平显着增加。因此,风险评分较低的患者从免疫治疗中获益更多.3种转录因子的组合可以评价TME中CD8+T细胞的耗尽状态，为评估HCC患者的TME和免疫治疗疗效奠定了基础。
