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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2005

01-05-2005 | Original Article

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

Authors: Hiroshi Nakashima, Akira Tasaki, Makoto Kubo, Hideo Kuroki, Kotaro Matsumoto, Masao Tanaka, Masafumi Nakamura, Takashi Morisaki, Mitsuo Katano

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2005

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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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Metadata
Title
Effects of docetaxel on antigen presentation-related functions of human monocyte-derived dendritic cells
Authors
Hiroshi Nakashima
Akira Tasaki
Makoto Kubo
Hideo Kuroki
Kotaro Matsumoto
Masao Tanaka
Masafumi Nakamura
Takashi Morisaki
Mitsuo Katano
Publication date
01-05-2005
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2005
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-004-0918-7

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