Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay

Abstract

Assessment of the chemosensitivity of dendritic cells (DC) may allow more rational development of combined chemotherapy and immunotherapy protocols. Human monocyte-derived DC generated reproducible results in the MTS (Owen's reagent) assay, which was then used to study DC survival after treatment with four different chemotherapy agents. DC preparations from three different donors were used per drug. DC were sensitive to doxorubicin (concentration range 0.1-50 μM) with variation in sensitivity between donors (IC50 244-1100 nM). The most extreme variation was seen for vinblastine (concentration range 250-0.025 μM with IC50 0.15-17.25 μM). In contrast, there was relative resistance to etoposide (concentration range 0.2-200 μM) and 5-fluorouracil (concentration range 0.7-7700 μM) with no toxicity seen until 50 μM and 770 μM respectively. The function of DC in allogeneic mixed leucocyte reactions closely paralleled results from the MTS assays. The differential sensitivity to chemotherapy agents did not appear to be due to expression of P-glycoprotein. These results suggest that etoposide or 5-fluorouracil is less likely to reduce the immunotherapeutic potential of DC and may be valuable in the design of prodrug activation therapy.