TY - JOUR
T1 - Effects of docetaxel on antigen presentation-related functions of human monocyte-derived dendritic cells
AU - Nakashima, Hiroshi
AU - Tasaki, Akira
AU - Kubo, Makoto
AU - Kuroki, Hideo
AU - Matsumoto, Kotaro
AU - Tanaka, Masao
AU - Nakamura, Masafumi
AU - Morisaki, Takashi
AU - Katano, Mitsuo
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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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U2 - 10.1007/s00280-004-0918-7
DO - 10.1007/s00280-004-0918-7
M3 - Article
C2 - 15726369
AN - SCOPUS:17644362285
SN - 0344-5704
VL - 55
SP - 479
EP - 487
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 5
ER -
