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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 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.
Filipe Amândio Brandão Sanches Vong Martins
Didier Trono, Priscilla Turelli, Evaristo Jose Planet Letschert, Filipe Amândio Brandão Sanches Vong Martins, Florian Huber, Olga Marie Louise Rosspopoff, Romain Forey, Sandra Eloise Kjeldsen, Cyril David Son-Tuyên Pulver, Joana Carlevaro Fita