PT  - JOURNAL ARTICLE
AU  - Christian M. Schürch
AU  - Salil S. Bhate
AU  - Graham L. Barlow
AU  - Darci J. Phillips
AU  - Luca Noti
AU  - Inti Zlobec
AU  - Pauline Chu
AU  - Sarah Black
AU  - Janos Demeter
AU  - David R. McIlwain
AU  - Nikolay Samusik
AU  - Yury Goltsev
AU  - Garry P. Nolan
TI  - Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front
AID  - 10.1101/743989
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 743989
4099  - http://biorxiv.org/content/early/2019/08/24/743989.short
4100  - http://biorxiv.org/content/early/2019/08/24/743989.full
AB  - 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 para ffin-em bedded 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 imm une functionality through interference in the concerted action of cells and spatial domains.