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固体瘤中的多细胞免疫生态型预测了免疫检查点抑制剂的实际治疗效益

Xuefeng Wang¹, Tingyi Li¹, Islam Eljilany²

¹Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

medRxiv : the preprint server for health sciences

|July 29, 2024

概括

这项研究揭示了独特的瘤微环境 (TME) 免疫细胞状态和生态系统,预测患者对免疫检查点抑制剂 (ICI) 治疗的反应. 识别这些TME生态型可以改善癌症免疫治疗患者的选择.

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:

瘤微环境 (TME) 对癌症的进展,转移和免疫规避至关重要.
了解TME的免疫架构对于预测瘤转移和对癌症治疗的反应至关重要.
免疫细胞状态 (CSs) 和它们在TME中的空间组织显著影响治疗结果.

研究的目的:

使用大量RNA测序数据,在瘤微环境 (TME) 中开发免疫细胞状态 (CSs) 的图书馆.
通过生态类型分析来解决TME中复杂的免疫架构.
在接受免疫检查点抑制剂 (ICI) 治疗的患者中调查免疫CS和多细胞生态系统的预后意义.

主要方法:

利用EcoTyper,一种机器学习 (ML) 框架,分析了来自1,610名癌症患者的分子数据.
将 ML 应用于来自 ORIEN 阿凡达队伍的现实数据,重点关注用免疫检查点抑制剂 (ICI) 治疗的患者.
进行了生存分析,以将已识别的TME生态型和免疫CS与患者结果相关联.

主要成果:

在泛癌分析中确定了一致的ICI特异性预后TME癌症生态型 (CE),包括淋巴细胞缺乏 (CE1) 和炎症性 (CE10) 类型.
在不同癌症类型中观察到CD8+和CD4+T细胞状态的一致分布模式.
发现生态型CE9与有利的生存率有关,而CE2与ORIEN ICI队列的不利结果有关. 特定于黑色素瘤的模型证实了较低风险得分的改善生存率. 生态型E3与较差的生存率有关.

结论:

研究结果为改进患者选择免疫疗法在现实临床环境中提供了洞察力.
结果可以指导开发针对特定TME生态型的新型治疗策略.
这项研究强调了特征TME免疫架构对于个性化癌症治疗的重要性.

关键词:

细胞图书馆细胞图书馆细胞状态细胞状态细胞类型细胞类型生态类型生态类型免疫治疗是一种免疫疗法.黑色素瘤是一种黑色素瘤.

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