Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer.

Animals Carcinogenesis / metabolism Cell Cycle Checkpoints Cell Line, Tumor Cell Polarity Cellular Senescence Chemokine CXCL2 / administration & dosage Humans Inflammation / pathology Macrophages / pathology Male Mice, Inbred C57BL Mice, Knockout Neoplasm Staging Neutralization Tests PTEN Phosphohydrolase / metabolism Prostatic Neoplasms / pathology Receptors, Interleukin-8B / antagonists & inhibitors Signal Transduction / drug effects Tumor Necrosis Factor-alpha / metabolism Tumor Suppressor Protein p53 / metabolism
immune response to cancer immunomodulation prostate cancer tumor associated macrophages tumor immunology

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
20 08 2019
Historique:
received: 05 12 2018
revised: 05 06 2019
accepted: 18 07 2019
entrez: 22 8 2019
pubmed: 23 8 2019
medline: 1 9 2020
Statut: ppublish

Résumé

Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment supporting tumorigenesis. TAMs re-education has been proposed as a strategy to promote tumor inhibition. However, whether this approach may work in prostate cancer is unknown. Here we find that Pten-null prostate tumors are strongly infiltrated by TAMs expressing C-X-C chemokine receptor type 2 (CXCR2), and activation of this receptor through CXCL2 polarizes macrophages toward an anti-inflammatory phenotype. Notably, pharmacological blockade of CXCR2 receptor by a selective antagonist promoted the re-education of TAMs toward a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in Pten

Identifiants

DOI: 10.1016/j.celrep.2019.07.068 PMID: 31433989 PMC: PMC6715643
pubmed: 31433989
pii: S2211-1247(19)30972-6
doi: 10.1016/j.celrep.2019.07.068
pmc: PMC6715643
pii:
doi:

Substances chimiques

Chemokine CXCL2 0
Receptors, Interleukin-8B 0
Tumor Necrosis Factor-alpha 0
Tumor Suppressor Protein p53 0
PTEN Phosphohydrolase EC 3.1.3.67

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2156-2168.e5

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Diletta Di Mitri (D)

Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.

Michela Mirenda (M)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Jelena Vasilevska (J)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Arianna Calcinotto (A)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Nicolas Delaleu (N)

Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway; Swiss Institute of Bioinformatics, Lausanne, Switzerland; 2C SysBioMed, 6646 Contra, Switzerland.

Ajinkya Revandkar (A)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Veronica Gil (V)

The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.

Gunther Boysen (G)

The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.

Marco Losa (M)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Simone Mosole (S)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Emiliano Pasquini (E)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Rocco D'Antuono (R)

Institute for Research in Biomedicine (IRB), 6500 Bellinzona, Switzerland.

Michela Masetti (M)

Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.

Elena Zagato (E)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Giovanna Chiorino (G)

Cancer Genomics Lab, Fondazione Edo ed Elvo Tempia, Via Malta, 3, 13900 Biella, Italy.

Paola Ostano (P)

Cancer Genomics Lab, Fondazione Edo ed Elvo Tempia, Via Malta, 3, 13900 Biella, Italy.

Andrea Rinaldi (A)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Letizia Gnetti (L)

Pathology Unit, University Hospital of Parma, 43126 Parma, Italy.

Mariona Graupera (M)

Vascular Signalling Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain; Program Against Cancer Therapeutic Resistance (ProCURE), Barcelona, Spain; CIBERONC, Madrid, Spain.

Ana Raquel Martins Figueiredo Fonseca (AR)

Vascular Signalling Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain; Program Against Cancer Therapeutic Resistance (ProCURE), Barcelona, Spain; CIBERONC, Madrid, Spain.

Ricardo Pereira Mestre (R)

Medical Oncology, Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland.

David Waugh (D)

Movember Centre of Excellence, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.

Simon Barry (S)

IMED Oncology AstraZeneca, Li KaShing Centre, Cambridge, UK.

Johann De Bono (J)

The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.

Andrea Alimonti (A)

Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Faculty of Medicine, Università della Svizzera Italiana, 1011 Lugano, Switzerland; Department of Medicine, University of Padua, 35131 Padua, Italy; Medical Oncology, Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland. Electronic address: andrea.alimonti@ior.usi.ch.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › Points de contrôle du cycle cellulaire › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Polarité de la cellule › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Vieillissement de la cellule › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Chimiokines › Protéines inflammatoires des macrophages › Chimiokine CXCL2 › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Diagnostic › Pronostic › Stadification tumorale › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Tests immunologiques › Tests sérologiques › Tests de neutralisation › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Phosphohydrolase PTEN › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux interleukines › Récepteurs à l'interleukine-8 › Récepteurs à l'interleukine-8B › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Re-education of Tumor-Associated Macrophages...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Re-education of Tumor-Associated Macrophages...