Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front
Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front
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DOI：
10.1016/j.cell.2020.07.005
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发表时间：
2020-09-03
期刊：
影响因子：
64.5
通讯作者：
Nolan, Garry P.
中科院分区：
文献类型：
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作者：
Schurch, Christian M.;Bhate, Salil S.;Nolan, Garry P.
抗肿瘤免疫需要免疫肿瘤微环境（iTME）组分之间有组织的、空间上细微的相互作用。了解这种有效与无效肿瘤控制的协调行为将促进免疫治疗。我们重新设计了石蜡包埋组织微阵列的索引联合检测（CODEX），使来自35名晚期结直肠癌（CRC）患者的140个组织区域的56种蛋白质标记物同时分析成为可能。我们确定了9个保守的，不同的细胞邻域（CN）-一个集合的组件特征的CRC iTME。PD-1（+）CD 4（+）T细胞仅在粒细胞CN内富集与高危患者亚群的生存率呈正相关。肿瘤和免疫CN偶联、T细胞和巨噬细胞CN碎片化以及CN间通讯中断与较差结局相关。这项研究提供了一个框架，询问如何复杂的生物过程，如抗肿瘤免疫，通过细胞和空间域的协同作用发生。
Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)-a collection of components characteristic of the CRC iTME. Enrichment of PD-1(+)CD4(+) T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains.