Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_1781FEB17DE0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer.
Périodique
Cell reports
Auteur(s)
Faget J., Groeneveld S., Boivin G., Sankar M., Zangger N., Garcia M., Guex N., Zlobec I., Steiner L., Piersigilli A., Xenarios I., Meylan E.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
12/12/2017
Peer-reviewed
Oui
Volume
21
Numéro
11
Pages
3190-3204
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1+ neutrophils to disease progression. Depletion experiments showed that Gr1+ cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration. Cxcl2 was produced mainly by neutrophils themselves in response to a factor secreted by Snail-expressing tumor cells. We therefore propose a vicious cycle encompassing neutrophils and Snail to maintain a deleterious tumor microenvironment.

Mots-clé
CXCL2, MegaClust, PD1, Snail, hypoxia, immune exclusion, immunotherapy, lung cancer, neutrophil, vascularization
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/01/2018 10:29
Dernière modification de la notice
16/09/2019 6:26
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