High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer.

cell-cell communication patient stratification single-cell sequencing therapy response tissue-resident neutrophils

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
12 12 2022
Historique:
received: 09 05 2022
revised: 26 08 2022
accepted: 06 10 2022
pubmed: 12 11 2022
medline: 16 12 2022
entrez: 11 11 2022
Statut: ppublish

Résumé

Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity with diverse immune cell infiltration patterns, which has been linked to therapy sensitivity and resistance. However, full understanding of how immune cell phenotypes vary across different patient subgroups is lacking. Here, we dissect the NSCLC tumor microenvironment at high resolution by integrating 1,283,972 single cells from 556 samples and 318 patients across 29 datasets, including our dataset capturing cells with low mRNA content. We stratify patients into immune-deserted, B cell, T cell, and myeloid cell subtypes. Using bulk samples with genomic and clinical information, we identify cellular components associated with tumor histology and genotypes. We then focus on the analysis of tissue-resident neutrophils (TRNs) and uncover distinct subpopulations that acquire new functional properties in the tissue microenvironment, providing evidence for the plasticity of TRNs. Finally, we show that a TRN-derived gene signature is associated with anti-programmed cell death ligand 1 (PD-L1) treatment failure.

Identifiants

pubmed: 36368318
pii: S1535-6108(22)00499-8
doi: 10.1016/j.ccell.2022.10.008
pmc: PMC9767679
pii:
doi:

Substances chimiques

B7-H1 Antigen 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1503-1520.e8

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Stefan Salcher (S)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Gregor Sturm (G)

Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Lena Horvath (L)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Gerold Untergasser (G)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Christiane Kuempers (C)

Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

Georgios Fotakis (G)

Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Elisa Panizzolo (E)

Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Agnieszka Martowicz (A)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria; Tyrolpath Obrist Brunhuber GmbH, Zams, Austria.

Manuel Trebo (M)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Georg Pall (G)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Gabriele Gamerith (G)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Martina Sykora (M)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Florian Augustin (F)

Department of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, Innsbruck, Austria.

Katja Schmitz (K)

Tyrolpath Obrist Brunhuber GmbH, Zams, Austria; INNPATH GmbH, Institute of Pathology, Innsbruck, Austria.

Francesca Finotello (F)

Institute of Molecular Biology, University of Innsbruck, Innsbruck, Austria; Digital Science Center, University of Innsbruck, Innsbruck, Austria.

Dietmar Rieder (D)

Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Sven Perner (S)

Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany; Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; German Center for Lung Research (DZL), Luebeck and Borstel, Germany.

Sieghart Sopper (S)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Dominik Wolf (D)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria.

Andreas Pircher (A)

Department of Internal Medicine V, Haematology & Oncology, Comprehensive Cancer Center Innsbruck (CCCI) and Tyrolean Cancer Research Institute (TKFI), Medical University of Innsbruck, Innsbruck, Austria. Electronic address: andreas.pircher@i-med.ac.at.

Zlatko Trajanoski (Z)

Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: zlatko.trajanoski@i-med.ac.at.

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