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高风险的清细胞细胞癌微环境含有前瘤免疫类型,缺乏特定的免疫检查点

Arti M Raghubar^1,2,3,4,5,6, Nicholas A Matigian⁷, Joanna Crawford⁵

¹Kidney Health Service, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

NPJ precision oncology

|September 11, 2023

概括

高危清细胞脏细胞癌 (ccRCC) 瘤已经耗尽了免疫细胞,不利于免疫疗法. 空间转录学揭示了这些瘤是免疫原的,但对免疫检查点抑制剂 (ICI) 没有反应.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
基因组学就是基因组学.

背景情况:

对高风险清细胞细胞癌 (ccRCC) 的外科手术免疫检查点抑制剂 (ICI) 试验产生了不一致的患者结果.
这表明瘤微环境 (TME) 免疫细胞组成和空间组织可能不利于ICI治疗.

研究的目的:

通过空间转录学来定义ccRCC TME中的免疫类型.
在ccRCC中识别与治疗反应相关的预测性免疫细胞特征.

主要方法:

空间转录组学测序 (ST-seq) 在新鲜的副瘤 (pTME),低级 (LG) 和高级 (HG) ccRCC组织样本上进行.
使用参考单细胞RNA和T细胞受体测序数据集确定了免疫细胞类型和状态 (耗尽/前瘤与不耗尽/抗瘤).

主要成果:

高度ccRCCTMEs表现出丰富的耗尽/前瘤免疫细胞,而没有增加常见检查点 (PD-1,PD-L1,CTLA4) 或血管基因的表达.
独特的HG TME特征包括表达HAVCR2和LAG3的亲瘤单细胞,具有干状原始基因表达的耗尽的CD8+ T细胞,以及表达TREM2的亲瘤巨/单细胞.

结论:

这项研究提供了人类ccRCC最大的ST-seq数据集,揭示了高风险ccRCCTMEs中的耗尽/前瘤免疫类型.
尽管具有免疫性,但HG ccRCC TMEs的特征是免疫细胞状态不有利于免疫检查点抑制剂治疗.

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