TY - JOUR TI - Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages AU - Thompson, Thornton W AU - Jackson, Benjamin T AU - Li, P Jonathan AU - Wang, Jiaxi AU - Kim, Alexander Byungsuk AU - Huang, Kristen Ting Hui AU - Zhang, Lily AU - Raulet, David H A2 - Yokoyama, Wayne M VL - 7 PY - 2018 DA - 2018/05/14 SP - e32919 C1 - eLife 2018;7:e32919 DO - 10.7554/eLife.32919 UR - https://doi.org/10.7554/eLife.32919 AB - NKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and humans. Here we show that in transplanted tumors and genetically engineered mouse cancer models, tumor-associated macrophages are induced to express the NKG2D ligand RAE-1δ. We find that a soluble factor produced by tumor cells is responsible for macrophage RAE-1δ induction, and we identify tumor-derived colony-stimulating factor-1 (CSF-1) as necessary and sufficient for macrophage RAE-1δ induction in vitro and in vivo. Furthermore, we show that induction of RAE-1δ on macrophages by CSF-1 requires PI3K p110α kinase signaling. Thus, production of CSF-1 by tumor cells leading to activation of PI3K p110α represents a novel cellular and molecular pathway mediating NKG2D ligand expression on tumor-associated macrophages. KW - NKG2D KW - macrophage KW - CSF-1 KW - tumor microenvironment JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -