Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front.
- Schürch CM Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: christian.m.schuerch@gmail.com.
- Bhate SS Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Barlow GL Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Phillips DJ Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Noti L Institute of Pathology, University of Bern, 3008 Bern, Switzerland.
- Zlobec I Institute of Pathology, University of Bern, 3008 Bern, Switzerland.
- Chu P Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Black S Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Demeter J Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- McIlwain DR Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Kinoshita S Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Samusik N Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Goltsev Y Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Nolan GP Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: gnolan@stanford.edu.
- 2020-08-09
Published in:
- Cell. - 2020
CODEX
FFPE
antitumoral immunity
cellular neighborhoods
colorectal cancer
immune checkpoints
immune tumor microenvironment
multiplexed imaging
tertiary lymphoid structures
tissue architecture
English
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1016/j.cell.2020.07.005
- PMID 32763154
- Persistent URL
- https://sonar.ch/global/documents/47078
Statistics
Document views: 46
File downloads:
- Full-text: 0