The local microenvironment drives activation of neutrophils in human brain tumors.

TNF-alpha angiogenesis brain metastasis glioblastoma glioma immune suppression myeloid niche neutrophil-to-lymphocyte ratio tumor immune microenvironment tumor immunology tumor microenvironment

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
12 Oct 2023
Historique:
received: 26 10 2022
revised: 11 07 2023
accepted: 31 08 2023
pubmed: 29 9 2023
medline: 29 9 2023
entrez: 28 9 2023
Statut: ppublish

Résumé

Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors in substantial numbers. However, their precise functions in different cancer types remain incompletely understood, including in the brain microenvironment. We therefore investigated neutrophils in tumor tissue of glioma and brain metastasis patients, with matched peripheral blood, and herein describe the first in-depth analysis of neutrophil phenotypes and functions in these tissues. Orthogonal profiling strategies in humans and mice revealed that brain tumor-associated neutrophils (TANs) differ significantly from blood neutrophils and have a prolonged lifespan and immune-suppressive and pro-angiogenic capacity. TANs exhibit a distinct inflammatory signature, driven by a combination of soluble inflammatory mediators including tumor necrosis factor alpha (TNF-ɑ) and Ceruloplasmin, which is more pronounced in TANs from brain metastasis versus glioma. Myeloid cells, including tumor-associated macrophages, emerge at the core of this network of pro-inflammatory mediators, supporting the concept of a critical myeloid niche regulating overall immune suppression in human brain tumors.

Identifiants

DOI: 10.1016/j.cell.2023.08.043 PMID: 37769657
pubmed: 37769657
pii: S0092-8674(23)00977-7
doi: 10.1016/j.cell.2023.08.043
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4546-4566.e27

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI165661
Pays : United States

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests D.C. has received consulting fees from Seed Biosciences S.A.; P.W. has provided consulting for Almax, Bayer, Sanofi, and Genentech. A.H. is a paid consultor for Flagship Pioneering, Inc. for matters unrelated to this study; M.E.H. has an advisory role at TME Pharma; J.A.J. received an honorarium for speaking at a Bristol Meyers Squibb research symposium and previously served on the scientific advisory board of Pionyr Immunotherapeutics.

Auteurs

Roeltje R Maas (RR)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Klara Soukup (K)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland.

Nadine Fournier (N)

Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; Translational Data Science Group, Swiss Institute of Bioinformatics, Lausanne 1011, Switzerland; Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1011, Switzerland.

Matteo Massara (M)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Sabine Galland (S)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Mara Kornete (M)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland.

Vladimir Wischnewski (V)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Joao Lourenco (J)

Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; Translational Data Science Group, Swiss Institute of Bioinformatics, Lausanne 1011, Switzerland.

Davide Croci (D)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland.

Ángel F Álvarez-Prado (ÁF)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Damien N Marie (DN)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland.

Johanna Lilja (J)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland.

Rachel Marcone (R)

Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; Translational Data Science Group, Swiss Institute of Bioinformatics, Lausanne 1011, Switzerland.

Gabriel F Calvo (GF)

Department of Mathematics & MOLAB-Mathematical Oncology Laboratory, University of Castilla-La Mancha, Ciudad Real 13071, Spain.

Rui Santalla Mendez (R)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Pauline Aubel (P)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Leire Bejarano (L)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Pratyaksha Wirapati (P)

Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1011, Switzerland.

Iván Ballesteros (I)

Program of Cardiovascular Regeneration, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.

Andrés Hidalgo (A)

Program of Cardiovascular Regeneration, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain; Vascular Biology and Therapeutics Program and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.

Andreas F Hottinger (AF)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Jean-Philippe Brouland (JP)

Department of Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne 1011, Switzerland.

Roy T Daniel (RT)

L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Monika E Hegi (ME)

L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.

Johanna A Joyce (JA)

Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland. Electronic address: johanna.joyce@unil.ch.

Classifications MeSH