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

First Author  Faget J Year  2017
Journal  Cell Rep Volume  21
Issue  11 Pages  3190-3204
PubMed ID  29241546 Mgi Jnum  J:254404
Mgi Id  MGI:6103916 Doi  10.1016/j.celrep.2017.11.052
Citation  Faget J, et al. (2017) Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer. Cell Rep 21(11):3190-3204
abstractText  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.
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