John, J, Ismail, M, Riley, C et al. (4 more authors) (2010) Differential effects of Paclitaxel on dendritic cell function. BMC Immunology, 11. 14. - . ISSN 1471-2172
Abstract
Background The potential utility of dendritic cells (DC) as cancer vaccines has been established in early trials in human cancers. The concomitant administration of cytotoxic agents and DC vaccines has been previously avoided due to potential immune suppression by chemotherapeutics. Recent studies show that common chemotherapy agents positively influence adaptive and innate anti-tumour immune responses. Results We investigated the effects of paclitaxel on human DC biology in vitro. DCs appear to sustain a significant level of resistance to paclitaxel and maintain normal viability at concentrations of up to 100 μmol. In some cases this resistance against paclitaxel is significantly better than the level seen in tumour cell lines. Paclitaxel exposure led to a dose dependent increase in HLA class II expression equivalent to exposure to lipopolysaccharide (LPS), and a corresponding increase in proliferation of allogeneic T cells at the clinically relevant doses of paclitaxel. Increase in HLA-Class II expression induced by paclitaxel was not blocked by anti TLR-4 antibody. However, paclitaxel exposure reduced the endocytic capacity of DC but reduced the expression of key pro-inflammatory cytokines such as IL-12 and TNFα. Key morphological changes occurred when immature DC were cultured with 100 μmol paclitaxel. They became small rounded cells with stable microtubules, whereas there were little effects on LPS-matured DC. Conclusions The effect of paclitaxel on human monocyte derived DC is complex, but in the clinical context of patients receiving preloaded and matured DC vaccines, its immunostimulatory potential and resistance to direct cytotoxicity by paclitaxel would indicate potential advantages to co-administration with vaccines.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © John et al; licensee BioMed Central Ltd. 2010 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | MHC CLASS-II; SIGNALING PATHWAY; BREAST-CANCER; CHEMOTHERAPY; TAXOL; EXPRESSION; ANTIGEN; DEATH; LIPOPOLYSACCHARIDE; CYCLOPHOSPHAMIDE |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Division of Epidemiology & Biostatistics (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Jul 2017 10:29 |
Last Modified: | 01 Mar 2019 11:48 |
Status: | Published |
Publisher: | BioMed Central |
Identification Number: | 10.1186/1471-2172-11-14 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:87606 |
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