To directly dissect the role of each immune component in human
tumor immunopathogenesis, we have studied the interaction between dendritic cells and T cells in the
tumor environment of patients with ovarian
carcinoma. We previously reported that functional plasmacytoid dendritic cells, but not functionally mature myeloid dendritic cells, accumulated in tumor microenvironments. We now show that
tumor ascites macrophage-derived dendritic cells induced
tumor-associated
antigen-specific CD8+ T cells with effector functions. Strikingly,
tumor ascites plasmacytoid dendritic cells induced
interleukin-10+ CCR7+ CD45RO+ CD8+ regulatory T cells. Four characteristics have been identified in
tumor plasmacytoid dendritic cell-induced CD8+ regulatory T cells: (a) induction of CD8+ regulatory T cells is independent of CD4+ CD25+ T cells; (b) CD8+ regulatory T cells significantly suppress myeloid dendritic cell-mediated
tumor-associated
antigen-specific T cell effector functions through
interleukin-10; (c) repetitive myeloid dendritic cell stimulation can recover CD8+ regulatory T cell-mediated poor T cell proliferation, but not T cell effector function; (d) CD8+ regulatory T cells express functional CCR7, and efficiently migrate with lymphoid homing
chemokine MIP-3beta. Primary suppressive CCR7+ CD45RO+ CD8+ T cells are found in the
tumor environment of patients with
ovarian cancers. Thus,
tumor-associated plasmacytoid dendritic cells contribute to the
tumor environmental immunosuppressive network. Collectively,
tumors manipulate
tumor microenvironmental dendritic cell subset distribution and function to subvert
tumor immunity. The data are relevant to understanding
tumor immunopathology as well as reevaluating
tumor immunotherapeutic strategies.