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

136 Pages Posted: 23 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Christian M. Schürch

Christian M. Schürch

Stanford University - Department of Microbiology and Immunology

Salil Bhate

Stanford University - Department of Microbiology and Immunology

Graham L. Barlow

Stanford University - Department of Microbiology and Immunology

Darci J. Phillips

Stanford University - Department of Microbiology and Immunology

Luca Noti

University of Bern - Institute of Pathology

Inti Zlobec

University of Bern - Institute of Pathology

Pauline Chu

Stanford University - Department of Microbiology and Immunology

Sarah Black

Stanford University - Department of Microbiology and Immunology

Janos Demeter

Stanford University - Baxter Laboratory in Stem Cell Biology

David R. McIlwain

Stanford University - Department of Microbiology and Immunology

Nikolay Samusik

Stanford University - Department of Microbiology and Immunology

Yury Goltsev

Stanford University - Department of Microbiology and Immunology

Garry Nolan

Stanford University - Department of Microbiology and Immunology

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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 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.

Keywords: Antitumoral immunity, cellular neighborhoods, CODEX, colorectal cancer, FFPE, immune checkpoints, immune tumor microenvironment, multiplexed imaging, tertiary lymphoid structures, tissue architecture

Suggested Citation

Schürch, Christian M. and Bhate, Salil and Barlow, Graham L. and Phillips, Darci J. and Noti, Luca and Zlobec, Inti and Chu, Pauline and Black, Sarah and Demeter, Janos and McIlwain, David R. and Samusik, Nikolay and Goltsev, Yury and Nolan, Garry, Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front (August 21, 2019). CELL-D-19-02119. Available at SSRN: https://ssrn.com/abstract=3440263 or http://dx.doi.org/10.2139/ssrn.3440263
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Christian M. Schürch

Stanford University - Department of Microbiology and Immunology ( email )

Stanford, CA 94305
United States

Salil Bhate

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Graham L. Barlow

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Darci J. Phillips

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Luca Noti

University of Bern - Institute of Pathology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Inti Zlobec

University of Bern - Institute of Pathology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Pauline Chu

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Sarah Black

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Janos Demeter

Stanford University - Baxter Laboratory in Stem Cell Biology

Stanford, CA 94305
United States

David R. McIlwain

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Nikolay Samusik

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Yury Goltsev

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Garry Nolan (Contact Author)

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

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