Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front
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Résumé
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.
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La notice
- Revue
- Cell
- Thématique
- Cancer Immunotherapy and Biomarkers
- Domaine
- Medicine
- Établissements canadiens
- —
- Organismes subventionnaires
- 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
- Mots-clés
- BiologyColorectal cancerImmunityCellular immunityCancerImmunologyCancer researchImmune systemGenetics
- Résumé présent dans OpenAlex
- oui