Ly6G+ neutrophils and polymorphonuclear-myeloid derived suppressor cells promote the survival of tumor cells

Myeloid derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells which suppress the immune system. Collectively a MDSC population is comprised of monocyte-like MDSC and polymorphonuclear MDSC (PMN-MDSC). The number of MDSC is increased with the presence of tumors. Our lab has previously shown that PMN-MDSC represent the majority of MDSC in tumor-bearing mice. We found that depletion of myeloid cells in vivo results in increased survival in a mouse model of multiple myeloma (MM). Direct co-culture of neutrophils (CD11b + Gr1 + cells from tumor-free mice) or PMN-MDSC (CD11b + Gr1 + cells from tumor-bearing mice) and MM cells increases the survival of the MM cells from chemotherapeutic-induced death. The protective effect is not due to cell-cell contact as neutrophil and PMN-MDSC supernatants also protect MM cells from cell death. This suggests that the factor protecting tumor cells is soluble. Results in the mouse were confirmed using human MM cells. Similar results have been replicated on breast cancer cells with neutrophils and PMN-MDSC. Several cytokines and growth factors, such as IL-6 and fibroblast growth factor, are implicated in chemoresistance. The role of these neutrophil and PMN-MDSC soluble factors and the identification of novel contributors to chemoresistance are under investigation.