瘤微环境中的T细胞耗尽预测算法,用于评估食道癌的预后分层和免疫治疗效果
Xiangyu Su1,2, Chenchun Fu2, Fei Liu3
1School of Medicine, Southeast University, Nanjing, China.
Environmental toxicology
|July 26, 2023
概括
基于T细胞枯竭 (TEX) 基因的新风险模型预测食道癌的预后和治疗反应. 该模型识别了可能从免疫疗法中受益的患者,并有助于了解耐药性.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 食道癌 (EC) 的预后和生存率很差,因此需要可靠的预后生物标志物.
- T细胞耗尽 (TEX) 与EC中更糟糕的结果和免疫透有关.
- 准确预测EC预后和治疗敏感度至关重要.
研究的目的:
- 开发和验证基于T细胞枯竭 (TEX) 相关基因的食道癌的预后模型.
- 调查基于TEX的风险模型,免疫细胞透和EC中的治疗敏感性之间的相关性.
- 探索PD-1在化学抵抗中的作用及其与EC中T细胞透的关系.
主要方法:
- 最小绝对收缩和选择操作员 (LASSO) 分析用于选预后模型的九个风险基因.
- 根据TEX相关的基因表达,患者被分为高风险和低风险组.
- 建立了耐药细胞系,以检查PD-1表达及其在CDDP耐药性中的作用;使用了qPCR和Western blot.
主要成果:
- 开发的基于TEX的风险模型显示了与EC预后,免疫细胞透和对化疗剂敏感性的显著相关性.
- 在抗CDDP的EC细胞中观察到PD-1表达的增加.
- 在耐药细胞中击败PD-1降低了CDDP耐药性和增加了细胞亡,这表明PD-1在药物耐药性中的作用.
结论:
- 基于TEX的风险模型作为食道癌的新预后生物标志物,预测患者的结果和治疗反应.
- 该模型与免疫细胞透水平和对药物治疗的敏感性有关.
- 降低PD-1的调节可能会增强药物敏感性和T细胞透在EC,高风险患者可能从免疫治疗中获益更多.
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