细胞免疫
结直肠癌
癌症
癌症研究
免疫系统
医学
免疫
免疫学
内科学
作者
Christian M. Schürch,Salil Bhate,Graham L. Barlow,Darci Phillips,Luca Noti,Inti Zlobec,Pauline Chu,Sarah Black,János Demeter,David R. McIlwain,Nikolay Samusik,Yury Goltsev,Garry P. Nolan
出处
期刊:Social Science Research Network
[Social Science Electronic Publishing]
日期:2019-01-01
被引量:3
摘要
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 optimized CO-Detection by indEXing (CODEX) for paraffin-embedded tissue microarrays, enabling profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers simultaneously. 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 complex biological processes, such as antitumoral immunity, demonstrating an example of how tumors can disrupt immune functionality through interference in the concerted action of cells and spatial domains.
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