Fas ligand deficiency impairs tumor immunity by promoting an accumulation of monocytic myeloid derived suppressor cells

The Fas receptor ligand FasL regulates immune cell levels by inducing apoptosis of Fas receptor-positive cells. Here we studied the impact of host FasL on tumor development in mice. Genetically targeting FasL in naive mice increased myeloid cell populations, but in marked contrast it reduced the levels of myeloid-derived suppressor cells (MDSC) in mice bearing LLC lung tumors. Analysis of the MDSC subset distribution revealed that FasL deficiency skewed cell populations toward the M-MDSC subset, which displays a highly immunosuppressive activity. Furthermore, tumor-bearing mice that were FasL-deficient displayed an enhanced proportion of tumor associated macrophages and T regulatory cells. Overall, the immunosuppressive environment produced by FasL targeting correlated with reduced survival of tumor-bearing mice. These results disclose a new role of FasL in modulating immunosuppressive cells.