Tumor Microenvironmental Conversion of Natural Killer Cells into Myeloid-Derived Suppressor Cells

How myeloid-derived suppressor cells (MDSC) emerge in the tumor environment remains unclear. Here, we report that GM-CSF can convert natural killer (NK) cells into MDSCs. When transferred into tumor-bearing mice, adoptively transferred NK cells lost their NK phenotype and were converted into Ly6C high Ly6G high MDSC. This conversion was abolished by exposure to IL-2 either in vitro or in vivo . Notably, we found that of the 4 maturation stages based on CD11b/CD27 expression levels, only the CD11b high CD27 high NK cells could be converted into CD11b + Gr1 + MDSC ex vivo . Transfer of CD27 high NK cells from tumor-bearing mice into tumor-bearing recipients was associated with conversion to MDSC in a manner associated with reduced numbers of CD11b high CD27 high and CD11b high CD27 low NK cell populations in the recipients. Our results identify a pathway of MDSC development from immature NK cells in tumor-bearing hosts, providing new insights into how tumor cells modulate their host immune microenvironment to escape immune surveillance. Cancer Res; 73(18); 5669–81. ©2013 AACR .