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头癌中三级淋巴结合物的空间动态:对免疫疗法反应的洞察

Habib Sadeghirad¹, James Monkman¹, Chin Wee Tan^1,2,3

¹Frazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.

Journal of translational medicine

|July 25, 2024

概括

在复发性/转移性头支状细胞癌 (R/M HNSCC) 中的三级淋巴体结构 (TLS) 对免疫检查点抑制剂 (ICI) 反应至关重要. 它们与瘤的接近表明结果更好,指导未来的R/M HNSCC治疗策略.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
基因组学就是基因组学.

背景情况:

复发性/转移性头支状细胞癌 (R/M HNSCC) 预后不佳,治疗选择有限.
免疫检查点抑制剂 (ICI) 是标准的护理,但由于瘤微环境 (TME) 的复杂性,其疗效具有变化.
三级淋巴体结构 (TLS) 正在成为免疫治疗反应的关键决定因素.

研究的目的:

调查TLS在R/M HNSCC对ICI反应中的作用.
了解TLS与ICI疗效相关的空间和分子特征.

主要方法:

使用多omics方法对两个R/M HNSCC患者队列的分析.
使用纳米链GeoMx数字空间分析仪进行有针对性的蛋白质基因分析.
在空间上解析了TLS和生殖中心 (GC) 的整个转录组概况.
使用Akoya Biosciences Phenocycler Fusion进行TLS的单细胞解析蛋白质基因分析.

主要成果:

ICI反应者显示"热瘤"表型与T淋巴细胞标记 (CD3,CD45,CD8) 和PD-L1上调.
抗原呈现细胞 (CD40,CD68,CD11c,CD163) 和HLA-DR在反应者中升高.
TLS分析显示免疫调节,免疫细胞招募和干扰素反应基因的增加.
更近的TLS-瘤距离与更好的ICI反应有显著的相关性 (H=9.28,p=0.026).

结论:

TLS在调节R/M HNSCC TME和影响ICI疗效方面发挥着重要作用.
空间解析的多主题提供了对ICI响应生物标志物的洞察力.
描述TME复杂性对于开发治疗策略和患者分层至关重要.

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