定义与黑色素瘤检查点免疫治疗反应相关的T细胞状态
Moshe Sade-Feldman1, Keren Yizhak2, Stacey L Bjorgaard3
1Massachusetts General Hospital Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Medicine, Massachusetts General Hospital, HMS, Boston, MA, USA.
Cell
|November 3, 2018
概括
研究人员在接受免疫检查点阻塞治疗的黑色素瘤患者中发现了两个CD8+ T细胞状态. 转录因子TCF7预测了积极的结果,为增强癌症免疫疗法提供了新的目标.
科学领域:
- 免疫学
- 癌症学
- 基因组学
背景情况:
- 免疫检查点阻断疗法改变了癌症治疗方法,
- 然而,许多患者没有反应或最终死于这种疾病,因此需要确定反应预测因子和治疗点.
- 了解瘤免疫微环境对于提高免疫疗法的有效性至关重要.
研究的目的:
- 确定与黑色素瘤免疫检查点治疗成功或失败相关的因素.
- 在瘤微环境中定义与临床结果相关的独特免疫细胞状态.
- 为了发现增强抗瘤免疫力的新目标.
主要方法:
- 在48名黑色素瘤患者的瘤样本中对16291个免疫细胞进行了单细胞RNA测序 (scRNA- seq).
- 用聚类分析来定义不同的CD8+T细胞状态.
- 使用免疫组织化学分析可视化瘤样本中的TCF7表达,并进行表观遗传学分析.
主要成果:
- 确定了两个不同的CD8+T细胞状态,与瘤回归或进展相关.
- 在独立的患者队列中,TCF7 (T细胞因子7) 在CD8+T细胞表达是积极临床结果的预测因子.
- 这些T细胞状态的表观遗传和克隆性被划定,揭示了耗尽的T细胞的潜在脆弱性.
结论:
- 这项研究揭示了与黑色素瘤检查点抑制剂反应相关的不同CD8+T细胞状态.
- TCF7是免疫治疗反应的潜在预测生物标志物.
- 针对耗尽的T细胞中的新组合可以增强抗瘤免疫力并改善患者的治疗结果.
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