SPECIFIC AUTOLOGOUS ANTIMELANOMA T-CELL RESPONSE IN-VITRO USING MONOCYTE-DERIVED DENDRITIC CELLS

Dendritic cells (DC) are antigen-pesenting cells initiating primary an d secondary immune responses. Since malignant tumors are able to escap e immunologic control, DC might be prime candidates to activate the im mune system against tumor cells. In an autologous system, a dynamic in teraction among monocyte-derived DC (MoDC), T lymphocytes, and tumor c ells obtained from melanoma patients could be noted. MoDC were generat ed from blood monocytes in the presence of GM-CSF, IL-4, and IFN-gamma . T cells were isolated either from peripheral blood or from lymph nod es. Melanoma cells were harvested from surgically removed tumor metast ases. They were then gamma-irradiated and co-cultured with autologous MoDC and T lymphocytes. After 5 days, the lymphocytes showed a high pr oliferative activity and the majority of them were CD8-positive. In fi ve cases tested, they revealed a high cytotoxic activity resulting in apoptosis of tumor cells. These findings suggest that MoDC are capable of initiating an effective specific anti-tumor response in a strictly autologous mixed lymphocyte tumor culture (MLTC), even though tumor-s pecific antigens had not been individually defined. Therefore (I) whol e melanoma cells can serve as a source of antigen, (II) monocyte-deriv ed dendritic cells may process and present melanoma-specific antigens resulting in a strong lymphocyte proliferation, (III) the majority of responding T lymphocytes are CD8-positive, and (IV) an acquired cytoto xic response eventually leads to apoptosis of the melanoma cells. The reaction demonstrated here permits to in vitro and quantitatively moni toring the effect of T cell directed immunotherapies such as the adopt ive immunotherapy of tumors.