Glioma-derived M-CSF and IL-34 license M-MDSCs to suppress CD8 + T cells in a NOS-dependent manner.

Currently there are no effective therapies for glioblastoma. Infiltrating myeloid cells contribute significantly to the immune suppressive tumor microenvironment that is characteristic of GBM. Monocytic myeloid derived suppressor cells are chief immune suppressive cells found in the glioma microenvironment. Understanding the mechanisms of M-MDSC differentiation and T cell suppression is imperative for generating therapies that target this tumor supportive cell population. In this study we found that glioma secreted CSF1R ligands, M-CSF and IL-34, license M-MDSCs to suppress CD8 T cells. These M-MDSCs partially utilize nitric oxide synthase to illicit their suppressive activity. However, spatial RNAseq points to glioma microenvironment niches driving M-MDSC heterogeneity. Our findings identify key regulators of differentiation and suppressive mechanisms of M-MDSCs and confirm the importance of targeting this cell population in glioma.