Unique features of co-existence of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer

In this study, using single cell RNAseq, cell mass-spectrometry, flow cytometry, and functional analysis, we characterized the heterogeneity of polymorphonuclear neutrophils (PMN) in cancer. We described three populations of PMN in tumor-bearing mice: classical PMN, polymorphonuclear myeloid derived suppressor cells (PMN-MDSC), and activated PMN-MDSC with potent immune suppressive activity. In spleens of mice, PMN-MDSC gradually replaced PMN during tumor progression. Activated PMN-MDSC were found only in tumors where they were present at the very early stages of the disease. These populations of PMN in mice could be separated based on the expression of CD14. In peripheral blood of cancer patients, we identified two distinct populations of PMN with characteristics of classical PMN and PMN-MDSC. Gene signature of tumor PMN-MDSC was similar to that in mouse activated PMN-MDSC and was closely associated with negative clinical outcome in cancer patients. Thus, we provided evidence that PMN-MDSC is a distinct population of PMN with unique features and potential for selective targeting opportunities Overall design: Single cell RNA-seq of polymorphonuclear neutrophils (PMN) from naïve and tumor burden (TB) mice Single cell RNA-seq of polymorphonuclear neutrophils (PMN) blood of healthy and tumor burden patients