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

2020· article· en· 1,045 citations· W3047081808 on OpenAlex· 10.1016/j.cell.2020.07.005

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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 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Cell
Topic
Cancer Immunotherapy and Biomarkers
Field
Medicine
Canadian institutions
Funders
National Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Human Genome Research InstituteJuno TherapeuticsU.S. Food and Drug AdministrationStanford Bio-XDefence Science and Technology LaboratoryHamilton Health Sciences FoundationNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungUniversity of OxfordParker Institute for Cancer ImmunotherapyU.S. Department of DefenseSilicon Valley Community FoundationUniversity of BernNational Institute of Allergy and Infectious DiseasesCelgeneNational Heart, Lung, and Blood InstitutePfizerBill and Melinda Gates FoundationNational Cancer InstituteKenneth Rainin FoundationCancer Research InstituteCancer Research UKNational Science Foundation
Keywords
BiologyColorectal cancerImmunityCellular immunityCancerImmunologyCancer researchImmune systemGenetics
Has abstract in OpenAlex
yes