Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells

Dendritic-cell (DQ trafficking and function in tumors is poorly characteriz ed, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migrati on and function, likely hindering specific immunity. The role of plasmacyto id DCs (DC2s) in tumor immunity is unknown. We show here that malignant hum an ovarian epithelial tumor cells express very: high levels of stromal-deri ved factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/ transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule -1 mediated preDC2 adhesion/transmig ration. Tumor preDC2s induced signific ant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor D Cs (preDC1s) were not detected. Tumors may weaken immunity by attracting pr eDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.