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Updated: Aug 19, 2026
Characterization of Human Monocyte-derived Dendritic Cells by Imaging Flow Cytometry: A Comparison between Two Monocyte Isolation Protocols
Published on: October 18, 2016
Effects of docetaxel on antigen presentation-related functions of human monocyte-derived dendritic cells
Hiroshi Nakashima1, Akira Tasaki, Makoto Kubo
1Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka City, 812-8582, Japan.
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-alpha and prostaglandin E(2).
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-1alpha and of mMo-DCs toward MIP-3beta. 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.
Insights
Docetaxel (TXT) at low therapeutic doses impairs the directional movement of dendritic cells (DCs), which are crucial for antigen presentation. This finding is important for understanding TXT
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Docetaxel (TXT) is a chemotherapy drug that stabilizes microtubules, impacting cellular functions.
- TXT is increasingly used with immunotherapy for advanced cancers.
- The effect of clinically relevant TXT concentrations on dendritic cell (DC) function is not well understood.
Purpose of the Study:
- To investigate the impact of TXT on human monocyte-derived dendritic cells (Mo-DCs) at concentrations below 10(-6) M.
- To assess TXT's influence on Mo-DC viability, phagocytosis, molecule expression, and motility.
- To determine how TXT affects antigen presentation-related functions of Mo-DCs.
Main Methods:
- Generated immature Mo-DCs (imMo-DCs) and mature Mo-DCs (mMo-DCs) in vitro.
- Treated Mo-DCs with varying concentrations of TXT.
- Assessed cellular viability, phagocytosis, and expression of antigen presentation molecules (CCR1, CCR7).
- Evaluated Mo-DC chemotactic motility towards chemokines (MIP-1alpha, MIP-3beta) and microtubule structure.
Main Results:
- TXT concentrations below 10(-7) M did not significantly affect Mo-DC viability, phagocytosis, or key molecule expression.
- TXT at concentrations below 10(-9) M significantly suppressed the directional motility of both imMo-DCs and mMo-DCs.
- No significant changes in microtubule structure were observed at TXT concentrations below 10(-8) M, but reduced podosome formation was noted in imMo-DCs.
Conclusions:
- Different concentrations of TXT differentially affect Mo-DC functions.
- TXT, even at relatively low therapeutic doses, disrupts the chemotactic motility of Mo-DCs.
- This disruption of Mo-DC motility may have implications for the efficacy of TXT-based cancer therapies, particularly when combined with immunotherapy.
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