The local microenvironment drives activation of neutrophils in human brain tumors

Roeltje R. Maas; Klara Soukup; Nadine Fournier; Matteo Massara; Sabine Galland; Mara Kornete; Vladimir Wischnewski; Joao Lourenco; Davide Croci; Ángel F. Álvarez-Prado; Damien N. Marie; Johanna Lilja; Rachel Marcone; Gabriel F. Calvo; Rui Santalla Mendez; Pauline Aubel; Leire Bejarano; Pratyaksha Wirapati; Iván Ballesteros; Andrés Hidalgo; Andreas F. Hottinger; Jean Philippe Brouland; Roy T. Daniel; Monika E. Hegi; Johanna A. Joyce

doi:10.1016/j.cell.2023.08.043

The local microenvironment drives activation of neutrophils in human brain tumors

Roeltje R. Maas, Klara Soukup, Nadine Fournier, Matteo Massara, Sabine Galland, Mara Kornete, Vladimir Wischnewski, Joao Lourenco, Davide Croci, Ángel F. Álvarez-Prado, Damien N. Marie, Johanna Lilja, Rachel Marcone, Gabriel F. Calvo, Rui Santalla Mendez, Pauline Aubel, Leire Bejarano, Pratyaksha Wirapati, Iván Ballesteros, Andrés HidalgoAndreas F. Hottinger, Jean Philippe Brouland, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

71 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	4546-4566.e27
Journal	Cell
Volume	186
Issue number	21
DOIs	https://doi.org/10.1016/j.cell.2023.08.043
Publication status	Published - 12 Oct 2023
Externally published	Yes

Keywords

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

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10.1016/j.cell.2023.08.043

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Maas, R. R., Soukup, K., Fournier, N., Massara, M., Galland, S., Kornete, M., Wischnewski, V., Lourenco, J., Croci, D., Álvarez-Prado, Á. F., Marie, D. N., Lilja, J., Marcone, R., Calvo, G. F., Santalla Mendez, R., Aubel, P., Bejarano, L., Wirapati, P., Ballesteros, I., ... Joyce, J. A. (2023). The local microenvironment drives activation of neutrophils in human brain tumors. Cell, 186(21), 4546-4566.e27. https://doi.org/10.1016/j.cell.2023.08.043

@article{485bee7cf4a34350a3d0d153d45d07b8,

title = "The local microenvironment drives activation of neutrophils in human brain tumors",

abstract = "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.",

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

author = "Maas, {Roeltje R.} and Klara Soukup and Nadine Fournier and Matteo Massara and Sabine Galland and Mara Kornete and Vladimir Wischnewski and Joao Lourenco and Davide Croci and {\'A}lvarez-Prado, {{\'A}ngel F.} and Marie, {Damien N.} and Johanna Lilja and Rachel Marcone and Calvo, {Gabriel F.} and {Santalla Mendez}, Rui and Pauline Aubel and Leire Bejarano and Pratyaksha Wirapati and Iv{\'a}n Ballesteros and Andr{\'e}s Hidalgo and Hottinger, {Andreas F.} and Brouland, {Jean Philippe} and Daniel, {Roy T.} and Hegi, {Monika E.} and Joyce, {Johanna A.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = oct,

day = "12",

doi = "10.1016/j.cell.2023.08.043",

language = "English",

volume = "186",

pages = "4546--4566.e27",

journal = "Cell",

issn = "0092-8674",

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number = "21",

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Maas, RR, Soukup, K, Fournier, N, Massara, M, Galland, S, Kornete, M, Wischnewski, V, Lourenco, J, Croci, D, Álvarez-Prado, ÁF, Marie, DN, Lilja, J, Marcone, R, Calvo, GF, Santalla Mendez, R, Aubel, P, Bejarano, L, Wirapati, P, Ballesteros, I, Hidalgo, A, Hottinger, AF, Brouland, JP, Daniel, RT, Hegi, ME & Joyce, JA 2023, 'The local microenvironment drives activation of neutrophils in human brain tumors', Cell, vol. 186, no. 21, pp. 4546-4566.e27. https://doi.org/10.1016/j.cell.2023.08.043

TY - JOUR

T1 - The local microenvironment drives activation of neutrophils in human brain tumors

AU - Maas, Roeltje R.

AU - Soukup, Klara

AU - Fournier, Nadine

AU - Massara, Matteo

AU - Galland, Sabine

AU - Kornete, Mara

AU - Wischnewski, Vladimir

AU - Lourenco, Joao

AU - Croci, Davide

AU - Álvarez-Prado, Ángel F.

AU - Marie, Damien N.

AU - Lilja, Johanna

AU - Marcone, Rachel

AU - Calvo, Gabriel F.

AU - Santalla Mendez, Rui

AU - Aubel, Pauline

AU - Bejarano, Leire

AU - Wirapati, Pratyaksha

AU - Ballesteros, Iván

AU - Hidalgo, Andrés

AU - Hottinger, Andreas F.

AU - Brouland, Jean Philippe

AU - Daniel, Roy T.

AU - Hegi, Monika E.

AU - Joyce, Johanna A.

PY - 2023/10/12

Y1 - 2023/10/12

N2 - 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.

AB - 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.

KW - TNF-alpha

KW - angiogenesis

KW - brain metastasis

KW - glioblastoma

KW - glioma

KW - immune suppression

KW - myeloid niche

KW - neutrophil-to-lymphocyte ratio

KW - tumor immune microenvironment

KW - tumor immunology

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85173495720&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.08.043

DO - 10.1016/j.cell.2023.08.043

M3 - Article

C2 - 37769657

AN - SCOPUS:85173495720

SN - 0092-8674

VL - 186

SP - 4546-4566.e27

JO - Cell

JF - Cell

IS - 21

ER -

The local microenvironment drives activation of neutrophils in human brain tumors

Abstract

Keywords

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