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Classification of Chemotherapeutic Agents Based on Their Differential In vitro Effects on Dendritic Cells

¹ Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas and ² Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, Ohio

Requests for reprints: Akira Takashima, Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, 3000 Arlington Avenue, Toledo, OH 43614. Phone: 419-383-5423; Fax: 419-383-3002; E-mail: akira.takashima{at}UToledo.edu.

Key Words: chemotherapy • pharmacology • dendritic cell

Despite the crucial roles dendritic cells (DC) play in host immunity against cancer, the pharmacologic effects of many chemotherapeutic agents have remained mostly unknown. We recently developed a DC biosensor clone by engineering the stable murine DC line XS106 to express the yellow fluorescent protein (YFP) gene under the control of interleukin (IL)-1β promoter. In this study, the resulting XS106 pIL1-YFP DC clone was used to screen 54 anticancer drugs. Each drug was tested at five concentrations (0.1–10 µmol/L) for its effects on YFP expression, cell viability, and granulocyte macrophage colony-stimulating factor–dependent growth. Our unbiased systematic screening unveiled a striking heterogeneity among the tested anticancer drugs in their effects on the three functional variables. Interestingly, 15 drugs induced significant YFP expression at subcytotoxic concentrations and were thus categorized as "DC-stimulatory" anticancer drugs. These drugs were subsequently found to induce at least one of the characteristic maturational changes in mouse bone marrow–derived DCs. For example, vinblastine, a prototypic drug of this class, induced the production of IL-1β, IL-6, and IL-12, increased surface expression of CD40, CD80, CD86, and MHC class II, and augmented T cell–stimulatory capacity of DCs. Not only do these results illustrate the differential pharmacologic effects of commonly used chemotherapeutic agents on DCs, they may also provide a conceptual framework for rationale-based selection and combination of anticancer drugs for clinical application. [Cancer Res 2009;69(17):6978–86]

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				H. Tanaka, H. Matsushima, A. Nishibu, B. E. Clausen, and A. Takashima Dual Therapeutic Efficacy of Vinblastine as a Unique Chemotherapeutic Agent Capable of Inducing Dendritic Cell Maturation Cancer Res., September 1, 2009; 69(17): 6987 - 6994. [Abstract] [Full Text] [PDF]