Accumulation of myeloid-derived suppressor cells (MDSCs) in aged hosts contribute to the age-related increase of susceptibility to murine breast adenocarcinoma and co-stimulatory molecules expressed in MDSCs are essential for MDSCs-mediated immune suppression. However, the co-stimulatory molecules that exert a direct effect on MDSCs-mediated age-dependent tumor susceptibility and the regulatory mechanism of their expression remain unclear. In the present study, we found that accumulation of MDSCs in aged mice was closely correlated with age-dependent enhanced growth of lung cancer. Further analysis revealed that B7-H1 was highly expressed in the MDSCs of 18-month but not in 2-month old mice. Accordingly, inhibition of B7-H1 with B7-H1 specific antibody significantly reactivated T cells and reduced the tumor progression mediated by MDSCs. In addition, IL-10 released from 18-month old mice stimulated the expression of B7-H1 on MDSCs. These results suggest that B7-H1 expressed on MDSCs is a novel target for reducing lung cancer susceptibility as the age increases.