Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front.

DOI
Publisher DOI
PubMed ID
32763154
Abstract
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.
Date Issued
2020-09-03
Publication Type
Article
Subject(s)
Subjects
CODEX FFPE antitumoral immunity cellular neighborhoods colorectal cancer immune checkpoints immune tumor microenvironment multiplexed imaging tertiary lymphoid structures tissue architecture
Language(s)
en
Author(s)
Schürch, Christian M
Bhate, Salil S
Barlow, Graham L
Phillips, Darci J
Chu, Pauline
Black, Sarah
Demeter, Janos
McIlwain, David R
Kinoshita, Shigemi
Samusik, Nikolay
Goltsev, Yury
Nolan, Garry P
Additional Credits
Journal
Cell
Publisher
Cell Press
ISSN
0092-8674
Related URL(s)
https://boris.unibe.ch/150073
Access(Rights)
open.access
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