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

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)479-487
Number of pages9
JournalCancer chemotherapy and pharmacology
Volume55
Issue number5
DOIs
Publication statusPublished - May 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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