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

Schürch, C. M., Bhate, S. S., Barlow, G. L., Phillips, D. J., Noti, L., Zlobec, I., ... & Samusik, N. (2020). Cell. PMID: 32763154 DOI: 10.1016/j.cell.2020.07.005

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

Online: https://www.cell.com/cell/fulltext/S0092-8674(20)30870-9

Issue: Cell. 2020 Sep 3;182(5):1341-1359.e19.

Highlights

  • FFPE-CODEX multiplexed tissue imaging of 56 markers in 140 tissues of 35 CRC patients
  • Cellular neighborhoods reveal spatial organization of the tumor microenvironment
  • Altered organization of tumor and immune components in low- versus high-risk patients
  • Local enrichment of PD-1+CD4+ T cells correlates with survival in high-risk patients

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.

 

AUTHOR AFFILIATIONS

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Institute of Pathology, University of Bern, 3008 Bern, Switzerland.
  6. Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  7. 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.

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