Next Generation Sequencing Facilitates Quantitative Analysis and Comparisions of Bone Marrow, Blood and Tumor-infiltrating Neutrophils

We report that tumor-infiltrating neutrophils are significantly different from their bone marrow and circulating neutrophils counterparts. We generated a heatmap clustering of the differentially expressed genes between the neutrophils from the three compartments, and identified four distinct gene clusters. Notably, genes in cluster 1 were down-regulated in tumor neutrophils, and comprised of genes involved in the adaptive immune response (GO:0002250). By contrast, genes in cluster 4 were up-regulated in tumor neutrophils, and consisted of genes involved in chemokine-mediated signalling pathway (GO:0070098) and positive regulation of cellular metabolic process (GO:0031325). We observed several cellular metabolic processes were up-regulated, suggesting a change in the metabolic signature of neutrophils that infiltrate the tumor. In conclusion, the distinct metabolic signature led us to hypothesize that the pronounced glycolytic profile of tumor-infiltrating neutrophils mediates pro-tumoral activity and PDAC progression. Examination of differential neutrophil populations in tumor-bearing mice