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

Schürch, Christian M. ; Bhate, Salil S. ; Barlow, Graham L. ; Phillips, Darci J. ; Noti, Luca ; Zlobec, Inti ; Chu, Pauline ; Black, Sarah ; Demeter, Janos ; McIlwain, David R. ; Kinoshita, Shigemi ; Samusik, Nikolay ; Goltsev, Yury ; Nolan, Garry P.

Cell, 2020-09, Vol.182 (5), p.1341-1359.e19 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front
Autor: Schürch, Christian M. ; Bhate, Salil S. ; Barlow, Graham L. ; Phillips, Darci J. ; Noti, Luca ; Zlobec, Inti ; Chu, Pauline ; Black, Sarah ; Demeter, Janos ; McIlwain, David R. ; Kinoshita, Shigemi ; Samusik, Nikolay ; Goltsev, Yury ; Nolan, Garry P.
Assuntos: antitumoral immunity ; B7-H1 Antigen - immunology ; Biomarkers, Tumor - immunology ; CD4-Positive T-Lymphocytes - immunology ; Cell Line, Tumor ; cellular neighborhoods ; CODEX ; colorectal cancer ; Colorectal Neoplasms - immunology ; Colorectal Neoplasms - therapy ; Female ; FFPE ; Humans ; immune checkpoints ; immune tumor microenvironment ; Immunotherapy - methods ; Male ; multiplexed imaging ; Neoplasm Invasiveness - immunology ; Resource ; tertiary lymphoid structures ; tissue architecture ; Tumor Microenvironment - immunology
É parte de: Cell, 2020-09, Vol.182 (5), p.1341-1359.e19
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These authors contributed equally
Descrição: 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. [Display omitted] •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 A multiplexed tissue imaging and computational analysis framework applied to colorectal cancer allows interrogation of how spatial organization of the immune tumor microenvironment is linked to clinical outcomes.
Editor: United States: Elsevier Inc
Idioma: Inglês

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

Schürch, Christian M. ; Bhate, Salil S. ; Barlow, Graham L. ; Phillips, Darci J. ; Noti, Luca ; Zlobec, Inti ; Chu, Pauline ; Black, Sarah ; Demeter, Janos ; McIlwain, David R. ; Kinoshita, Shigemi ; Samusik, Nikolay ; Goltsev, Yury ; Nolan, Garry P.

United States: Elsevier Inc

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