Summary
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.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Albert, ML, Sauter, B & Bhardwaj, N (1998). Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTL. Nature 392: 86–89.
Austyn, JM (1998). Dendritic cells. Curr Opin Hematol 5: 3–15.
Bender, A, Sapp, M, Schuler, G, Steinman, RM & Bhardwaj, N (1996). Improved methods for the generation of dendritic cells from non-proliferating progenitors in human blood. J Immunol Methods 196: 121–135.
Berger, W, Elbling, L, Hauptmann, E & Micksche, M (1997). Expression of the multidrug resistance-associated protein (MRP) and chemoresistance of human non-small cell lung cancer cells. Int J Cancer 73: 84–93.
Cory, AH, Owen, TC, Barltrop, JA & Cory, JG (1991). Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun 3: 207–212.
Fraile, RJ, Baker, LH, Buroker, TR, Horwitz, J & Vaitkevicius, VK (1980). Pharmacokinetics of 5-fluorouracil administered orally, by rapid intravenous and by slow infusion. Cancer Res 40: 2223–2228.
Greene, RF, Collins, JM, Jenkins, JF, Speyer, JL & Myers, CE (1983). Plasma pharmacokinetics of Adriamycin and Adriamycinol: implications for the design of in vitro experiments and treatment protocols. Cancer Res 43: 3417–3421.
Henwood, JM & Brogden, RN (1990). Etoposide: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in combination chemotherapy of cancer. Drugs 39: 438–490.
Melcher, A, Todryk, S, Hardwick, N, Ford, M, Michael, J & Vile, RG (1998). Tumour immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med 4: 581–587.
Mullen, CA, Kilstrup, M & Blaese, RM (1992). Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. Proc Natl Acad Sci 89: 33–37.
Nelson, RI, Dyke, RW & Root, MA (1980). Comparative pharmacokinetics of vindesine, vincristine and vinblastine in patients with cancer. Cancer Treat Rev 7: 17–24.
Nestle, FO, Alijagic, S, Gilliet, M, Sun, Y, Grabbe, S, Dummer, R, Burg, G & Schadendorf, D (1998). Vaccination of melanoma patients with peptide- or tumour lysate-pulsed dendritic cells. Nat Med 4: 328–335.
Randolph, GJ, Beaulieu, S, Pope, M, Sugawara, I, Hoffman, L, Steinman, RM & Muller, WA (1998). A physiological function for p-glycoprotein during the migration of dendritic cells from skin via afferent lymphatic vessels. Proc Natl Acad Sci USA 95: 6942–6929.
Romani, N, Reider, D, Heuer, M, Ebner, S, Kampgen, E, Eibl, B, Niederwieser, D & Schuler, G (1996). Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196: 137–151.
Rubartelli, A, Poggi, A & Zocchi, MR (1997a). The selective engulfment of apoptotic bodies by dendritic cells is mediated by the αβ3 integrin and requires intracellular and extracellular calcium. Eur J Immunol 27: 1893–1900.
Rubartelli, A, Poggi, A & Zocchi, MR (1997b). The selective engulfment of apoptotic bodies by dendritic cells is mediated by the alpha(v)beta3 integrin and requires intracellular and extracellular calcium. Eur J Immunol 27: 1893–1900.
Author information
Authors and Affiliations
Additional information
Dr David Chao is a Medical Research Council Clinical Training Fellow.
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Chao, D., Bahl, P., Houlbrook, S. et al. Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay. Br J Cancer 81, 1280–1284 (1999). https://doi.org/10.1038/sj.bjc.6694366
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.bjc.6694366
Keywords
This article is cited by
-
Plasmacytoid dendritic cells are short-lived: reappraising the influence of migration, genetic factors and activation on estimation of lifespan
Scientific Reports (2016)
-
Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations
Journal of Translational Medicine (2009)
