在T细胞中以ADGRE5为中心的Tsurv模型识别了对新辅助性癌症免疫疗法的响应者
Jian Li1, Zhouwenli Meng1, Zhengqi Cao1
1Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Frontiers in immunology
|February 12, 2024
概括
研究人员确定了一种类似干细胞T细胞集群 (survT),与新辅助抗PD1免疫疗法后的主要病理反应 (MPR) 有关. 基于ADGRE5的预测模型被开发出来,以识别可能达到MPR的患者,帮助治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 计算生物学 计算生物学
背景情况:
- 新辅助抗PD1免疫疗法改善了生存率,但缺乏识别患者实现重大病理反应 (MPR) 或克服耐药性的方法.
- 准确识别MPR对于优化外科手术期间的策略和癌症治疗患者的结果至关重要.
研究的目的:
- 在应对新辅助抗PD1免疫治疗时剖析MPR的细胞机制.
- 开发一个预测模型来识别将实现MPR的患者.
- 了解非MPR患者的耐药性机制.
主要方法:
- 综合公开可用的免疫检查点抑制剂 (ICI) 单细胞 (sc) 数据用于发现.
- 开发了蜂通信分析和基于VIPER的SCENIC管道.
- 在非小细胞肺癌 (NSCLC) ICI队列得分数据和小鼠模型 (批量-RNA-seq,Chip-seq,CYTOF) 中验证的发现.
- 利用3D原生水凝模型和机器学习 (ML) 来构建一个以ADGRE5为中心的Tsurv模型.
主要成果:
- 鉴定了一种MPR扩张的T细胞元集群 (MPR-E),其特征是具有增强STAT5-ADGRE5轴信号的干状CD8+T细胞 (survT).
- 在MPR-E中使用在小鼠模型中的多omics分析确认了具有沉默功能和免疫检查点的survT细胞.
- 使用ML开发了一个以ADGRE5为中心的Tsurv模型,在各种癌症类型的TME和外周血液单核细胞 (PBMC) 中得到验证,预测MPRICI前后治疗.
- 通过STAT5-IL32揭示了ICI刺激的ADGRE5上调,增强了survT干细胞和细胞毒性.
结论:
- 该研究提供了关于MPR在新辅助抗PD1治疗中的机制的见解.
- 为识别非MPR患者,开发了一种有效的以ADGRE5为中心的Tsurv模型.
- 这些发现可以指导开发新的治疗策略,以提高免疫疗法反应率.
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