期刊
CELL REPORTS
卷 21, 期 11, 页码 3190-3204出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.11.052
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资金
- Swiss National Science Foundation
- National Centre of Competence in Research (NCCR) Molecular Oncology
- Swiss Cancer League [KLS-2885-02-2012]
- Chercher et Trouver Foundation
- Molecular Life Sciences'' grant from the ISREC Foundation
- Nuovo Soldati Foundation
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 antiPD1 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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