尿路和头瘤微环境中的空间关系预测了对组合免疫检查点抑制剂的反应
Alberto Gil-Jimenez1,2, Nick van Dijk3, Joris L Vos4,5
1Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Nature communications
|March 22, 2024
概括
免疫细胞的空间关系,而不是密度,预测了尿道癌中对免疫检查点抑制剂 (ICI) 的反应. 特定的免疫细胞与癌细胞的接近表明反应,而另一些表明对ICI治疗没有反应.
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:
- 免疫检查点抑制剂 (ICI) 在尿道癌 (UC) 中表现有前途,但响应预测仍然具有挑战性.
- 瘤微环境 (TME) 的特征,特别是免疫细胞的存在,与ICI疗效有关.
- 对于TME特征与对ICI联合治疗的反应之间的确切关系尚不清楚.
研究的目的:
- 研究TME免疫细胞密度和空间关系 (SRs) 之间的关联,以及UC中术前组合ICI治疗的反应.
- 为了确定SRs,除了简单的细胞密度之外,是否可以作为ICI反应的预测生物标志物.
主要方法:
- 多重体免疫光被用来量化24个基线UC瘤样本中的免疫细胞密度和SRs.
- 使用韦布尔分布建模空间关系,分析免疫细胞和癌细胞之间的近邻距离.
- 评估了TME指标 (密度和SRs) 与对伊皮利木巴 + 尼沃木巴的反应之间的关联.
主要成果:
- 仅仅免疫细胞密度并没有区分ICI治疗的响应者和不响应者.
- 特定的SR指标,如CD8+ T细胞和癌细胞附近的巨细胞,与治疗反应有关.
- CD8+ T 细胞与 B 细胞的聚类被确定为不响应的标志物,在头癌队列中得到验证.
结论:
- 免疫细胞在TME内的空间关系是UC中ICI组合疗法的反应的关键决定因素.
- 与细胞密度相比,SR指标,特别是细胞毒性免疫细胞与瘤细胞的接近,提供了优越的预测价值.
- 这些发现突出了SRs作为可靠的生物标志物,用于预测预手术组合ICI的反应.
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