Myeloid-derived suppressor cells (MDSCs) suppress anti-tumor immune cells, which promote tumor progression. Although MDSCs are considered as potential targets of cancer immunotherapy, the mechanisms of immunosuppressive function of MDSCs still remains unclear. Although several reports have revealed that granulocyte colony-stimulating factor (G-CSF) enhanced the pro-tumor effects of MDSCs, the direct effects of G-CSF on MDSCs are unrevealed. In this study, we found that G-CSF-conditioned MDSCs exhibited enhanced immunosuppressive activity than those differentiated without G-CSF. Since g-glutamyltransferase (GGT) 1 is supposed to be a candidate for the enhanced immunosuppressive function of MDSCs by RNA-seq analysis, we found that GGsTop, a GGT inhibitor, cancelled the enhancement of immunosuppressive activity of MDSCs by G-CSF.
G-CSF is clinically used for the prevention and therapy of febrile neutropenia (FN). We found that the tumor progression in the FN mouse models was promoted by G-CSF and that GGsTop prevented this tumor progression. On the other hand, GGsTop did not inhibit the increase of neutrophils by G-CSF, suggesting that GGT1 inhibition did not affect to therapeutic effect of G-CSF. Together, these results suggest that the enhanced immunosuppressive function of MDSCs through GGT1. These findings should contribute to the development of safer more effective cancer immunotherapy.