在肿瘤微环境（TME）中，CD8 T细胞由于肿瘤抗原的持续刺激而呈现阶段性衰竭。评估CD8 T细胞的状态并逆转其耗竭是评价肿瘤患者预后和治疗效果的关键。本研究的目的是建立一个预后特征，可以有效预测肝细胞癌（HCC）患者的预后和对免疫治疗的反应。我们使用单变量 Cox 分析从癌症基因组图谱数据集中获取与 CD8 T 细胞耗竭相关的转录因子。然后，使用 LASSO Cox 回归构建转录因子碱性亮氨酸拉链 ATF 样转录因子、脱中皮蛋白和调节 T 细胞耗竭的 T-box 蛋白 21 的预后特征。通过逆转录定量聚合酶链反应检测 23 对 HCC 和癌旁组织中 3 个转录因子 mRNA 的相对表达水平，并在癌症基因组图谱数据集内部和国际癌症基因组联盟数据集中进行内部验证。 Cox回归分析显示风险评分是一个独立的预后变量。高危组的总生存率显着低于低危组。低风险组的免疫评分、矩阵评分和ESTIMATE评分较高，且低风险组中大多数免疫检查点基因的表达水平显着升高。因此，风险评分较低的患者从免疫治疗中获益更多。 3个转录因子的组合可以评估TME中CD8 T细胞的耗竭状态，为评估HCC患者的TME和免疫治疗疗效奠定基础。版权所有©2024作者。由 Wolters Kluwer Health, Inc. 出版

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.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.