Authors: Christian M Schürch1, Salil S Bhate2 Graham L Barlow3, Darci J Phillips4, Luca Noti5, Inti Zlobec5, Pauline Chu3, Sarah Black3, Janos Demeter6, David R McIlwain3, Nikolay Samusik6, Yury Goltsev3, Garry P Nolan7
Issue: Cell. 2020 Sep 3;182(5):1341-1359.e19.
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.