Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice.

Abstract

Subclinical doses of Paclitaxel (PTX) given 1day prior to a HER-2/neu (neu)-targeted, granulocyte-macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu(+) tumor growth in tolerized HER-2/neu (neu-N) mice. We demonstrate that co-administration of PTX and Cyclophosphamide (CY) synergizes to slow tumor growth, and that in vitro, DC precursors exposed to PTX before LPS maturation results in greater co-stimulatory molecule expression, IL-12 production, and the ability to induce CD8(+) T cells with enhanced lytic activity against neu(+) tumors. PTX treatment also enhances maturation marker expression on CD11c(+) DCs isolated from vaccine-draining lymph nodes. Ex vivo, these DCs activate CD8(+) T cells with greater lytic capability than DC's from vaccine alone-treated neu-N mice. Finally, PTX treatment results in enhanced antigen-specific, IFN-gamma-secreting CD8(+) T cells in vivo. Thus, administration of PTX with a tumor vaccine improves T cell priming through enhanced maturation of DC.

• Authors: Lukas W Pfannenstiel, Samuel S K Lam, Leisha A Emens, Elizabeth M Jaffee, Todd D Armstrong
• Journal: Cellular immunology (Cell Immunol) Vol. 263 Issue 1 Pg. 79-87 ( 2010) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 20346445 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• Antigens, Neoplasm
• Cancer Vaccines
• Cytokines
• Toll-Like Receptor 4
• Granulocyte-Macrophage Colony-Stimulating Factor
• Cyclophosphamide
• Receptor, ErbB-2
• Paclitaxel

Topics

• Animals
• Antigens, CD (biosynthesis)
• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cancer Vaccines
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Chemotherapy, Adjuvant
• Cyclophosphamide (administration & dosage, pharmacology)
• Cytokines (genetics, metabolism)
• Cytotoxicity, Immunologic (drug effects)
• Dendritic Cells (drug effects, immunology, metabolism, pathology)
• Drug Therapy, Combination
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Transgenic
• Neoplasm Transplantation
• Neoplasms (immunology, therapy)
• Paclitaxel (pharmacology)
• Receptor, ErbB-2 (immunology)
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)
• Tumor Burden (drug effects)