Activated dendritic cells from bone marrow cells of mice receiving cytokine-expressing tumor cells are associated with the enhanced survival of mice bearing syngeneic tumors

Dendritic cells (DCs), which phagocytose antigens and subsequently prolifer ate and migrate, may be the most powerful antigen-presenting cells that act ivate naive T cells. To determine their role in the immune response to tumo rs, we used WEHI-3B murine leukemia cells transduced with adenovirus vector s expressing cytokines. We found that mixtures of irradiated cells expressi ng granulocyte-macrophage colony-stimulating factor (GM-CSF) plus those exp ressing interleukin-4 (IL-4) or tumor necrosis factor alpha (TNF alpha) pro tected mice against WEHI-3B-induced leukemias. When bone marrow mononuclear cells (BMMNCs) obtained from mice that had been injected with irradiated, cytokine-expressing tumor cells were injected into tumor-bearing mice, the survival of the latter was significantly prolonged; the longest survival wa s observed in mice receiving BMMNCs containing an increased number of DCs f rom animals injected with a mixture of tumor cells expressing GM-CSF with t hose expressing IL-4. Assay for antileukemic effects in spleen of the latte r animals showed specific antitumor cytotoxicity against WEHI-3B, suggestin g that DCs from donor mice activate specific T cells in the tumor-bearing r ecipients. These results suggest that the infusion of syngeneic BMMNCs stim ulated with cytokine-expressing tumor cells may be effective in treating ce rtain types of tumors. (C) 1999 by The American Society of Hematology.