Analysis of gene expression from CD45neg cells of lung tumors upon neutrophil depletion or not. Mus musculus

Interrogating the tumor immune compartment generates new prognostic and treatment modalities. We used the poorly immunogenic oncogenic Kras driven mouse model of lung cancer, to challenge the predictive value of an immune signature, using a new algorithm called MegaClust. It highlighted a predominant negative impact of neutrophil infiltration on multiple immune populations. Human samples and depletion experiments in mice revealed that neutrophils promote tumor growth by altering angiogenesis, associated to increased PI3K/Akt/mTOR signaling in tumor cells and profound immunosubversion. Together with blood vessel spreading and normalization, neutrophil depletion was associated with T cell redistribution into tumor mass and sensitized tumors to anti-PD1 immunotherapy in this refractory model. Our observations illustrate a mechanism of immune exclusion protecting tumor cells from destruction that relies on neutrophil infiltration Overall design: Comparison of samples between anti-Ly6G and control IgG treatment