Dynamics of migration patterns of polymorphonuclear myeloid-derived suppressor cells during tumor progression

Abstract

Abstract Although recruitment of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to the tumor site is well documented, little is known about their migration patterns within bone marrow in tumor progression. We found that the activation of neutrophils migration in cancer is a two-phase process. The first phase was characterized by the accumulation of a previously uncharacterized population of neutrophils that lack immunosuppressive activity but display a potent ability to spontaneously migrate, whereas the later phase is associated with accumulation of neutrophils with typical features of PMN-MDSC with low migratory activity in the bone marrow of mice with various subcutaneous (ectopic) tumors and in mice with advanced orthotopic lung cancer. Mechanistically, PM-LCs displayed increased metabolic flux through oxidative phosphorylation and glycolysis and have more ATP than that of control neutrophils. However, PMN-MDSC were indistinguishable from neutrophils from tumor-free mice in their metabolic activity. In line with studies of mice, CD15+ neutrophils exhibited greater spontaneous migration than that of PMN-MDSCs from the same patient with cancer. These results elucidate the dynamic changes that neutrophils undergo in cancer.