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

Abstract : 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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https://hal.umontpellier.fr/hal-02430851
Contributeur : Amandine Michel-Avella <>
Soumis le : mardi 7 janvier 2020 - 15:41:57
Dernière modification le : mercredi 8 janvier 2020 - 01:47:47

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Julien Faget, Svenja Groeneveld, Gaël Boivin, Martial Sankar, Nadine Zangger, et al.. Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer. Cell Reports , Elsevier Inc, 2017, 21 (11), pp.3190-3204. ⟨10.1016/j.celrep.2017.11.052⟩. ⟨hal-02430851⟩

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