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Effects of docetaxel on antigen presentation-related functions of human monocyte-derived dendritic cells

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Abstract

Purpose

Docetaxel (TXT) is a unique chemotherapeutic agent that has been approved for treating various types of malignancies. TXT stabilizes microtubule assembly in cells and causes various dysfunctions of microtubule-dependent cellular events. Patients with advanced malignancies are beginning to receive TXT in combination with immunotherapy; however, the influence of TXT at clinically achievable serum concentrations (less than 10−6 M) on antigen presentation-related functions of human monocyte-derived dendritic cells (Mo-DCs) remains unclear.

Methods

Immature Mo-DCs (imMo-DCs) were generated from peripheral blood monocytes with interleukin-4 and granulocyte-macrophage colony-stimulating factor in vitro. Mature Mo-DCs (mMo-DCs) were induced from imMo-DCs with tumor necrosis factor-α and prostaglandin E2.

Results

TXT at concentrations lower than 10−7 M did not significantly affect cellular viability, phagocytosis, or expression of antigen presentation-related molecules of Mo-DCs. In contrast, TXT at concentrations lower than 10−9 M significantly suppressed directional motility of imMo-DCs toward MIP-1α and of mMo-DCs toward MIP-3β. However, TXT had no effect on either CCR1 expression by imMo-DCs or CCR7 expression by mMo-DCs. No gross changes in the microtubule skeleton were evident by immunofluorescence microscopy after treatment with TXT at less than 10−8 M. However, reduced numbers of imMo-DCs with podosomes localized primarily in one cell region were observed.

Conclusions

The present results indicate that different concentrations of TXT influence antigen presentation-related functions differently. In particular, TXT at relatively low therapeutic doses disrupts chemotactic motility of Mo-DCs.

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Authors and Affiliations

  1. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka City, 812-8582, Japan

    Hiroshi Nakashima, Akira Tasaki, Makoto Kubo, Hideo Kuroki, Kotaro Matsumoto, Masafumi Nakamura, Takashi Morisaki & Mitsuo Katano

  2. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka City, 812-8582, Japan

    Masao Tanaka

Authors
  1. Hiroshi Nakashima
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  2. Akira Tasaki
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  4. Hideo Kuroki
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Correspondence to Mitsuo Katano.

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Nakashima, H., Tasaki, A., Kubo, M. et al. Effects of docetaxel on antigen presentation-related functions of human monocyte-derived dendritic cells. Cancer Chemother Pharmacol 55, 479–487 (2005). https://doi.org/10.1007/s00280-004-0918-7

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  • DOI: https://doi.org/10.1007/s00280-004-0918-7

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