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

Faget, Julien; Groeneveld, Svenja; Boivin, Gael; Sankar, Martial; Zangger, Nadine; Garcia, Miguel; Guex, Nicolas; Zlobec, Inti; Steiner, Loïc; Piersigilli, Alessandra; Xenarios, Ioannis; Meylan, Etienne (2017). Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer. Cell reports, 21(11), pp. 3190-3204. Cell Press 10.1016/j.celrep.2017.11.052

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology

UniBE Contributor:

Zlobec, Inti and Piersigilli, Alessandra

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2211-1247

Publisher:

Cell Press

Language:

English

Submitter:

Inti Zlobec

Date Deposited:

31 Jan 2018 15:29

Last Modified:

23 Oct 2019 21:00

Publisher DOI:

10.1016/j.celrep.2017.11.052

PubMed ID:

29241546

Uncontrolled Keywords:

CXCL2 MegaClust PD1 Snail hypoxia immune exclusion immunotherapy lung cancer neutrophil vascularization

BORIS DOI:

10.7892/boris.110618

URI:

https://boris.unibe.ch/id/eprint/110618

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